Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Enzymes which transfer coenzyme A moieties from acyl- or acetyl-CoA to various carboxylic acceptors forming a thiol ester. Enzymes in this group are instrumental in ketone body metabolism and utilization of acetoacetate in mitochondria. EC 2.8.3.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
DNA sequences encoding the beta chain of the T-cell receptor. The genomic organization of the TcR beta genes is essentially the same in all species and is similar to the organization of Ig genes.
Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Glycoproteins found on the membrane or surface of cells.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
Antibodies produced by a single clone of cells.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
DNA sequences encoding the alpha chain of the T-cell receptor. The genomic organization of the TcR alpha genes is essentially the same in all species and is similar to the organization of Ig genes.
A costimulatory receptor that is specific for INDUCIBLE T-CELL CO-STIMULATOR LIGAND. The receptor is associated with a diverse array of immunologically-related effects including the increased synthesis of INTERLEUKIN 10 in REGULATORY T-LYMPHOCYTES and the induction of PERIPHERAL TOLERANCE.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
An encapsulated lymphatic organ through which venous blood filters.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
DNA sequences, in cells of the T-lymphocyte lineage, that code for T-cell receptors. The TcR genes are formed by somatic rearrangement (see GENE REARRANGEMENT, T-LYMPHOCYTE and its children) of germline gene segments, and resemble Ig genes in their mechanisms of diversity generation and expression.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Substances that are recognized by the immune system and induce an immune reaction.
Adolescent hospitalized for short term care.
Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.
Established cell cultures that have the potential to propagate indefinitely.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Functional inactivation of T- or B-lymphocytes rendering them incapable of eliciting an immune response to antigen. This occurs through different mechanisms in the two kinds of lymphocytes and can contribute to SELF TOLERANCE.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors.
The major group of transplantation antigens in the mouse.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
A B7 antigen that binds specifically to INDUCIBLE T-CELL CO-STIMULATOR PROTEIN on T-CELLS. It provides a costimulatory signal for T-cell proliferation and cytokine secretion.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
The number of LYMPHOCYTES per unit volume of BLOOD.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
A tumor necrosis family receptor with specificity for OX40 LIGAND. It is found on the surface of activated T-LYMPHOCYTES where it plays a role in enhancing cytokine production and proliferation of CD4-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Sites on an antigen that interact with specific antibodies.
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.
Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A family of cell-surface proteins found on ANTIGEN-PRESENTING CELLS. B7 antigens are ligands for specific cell surface receptor subtypes found on T-CELLS. They play an immunomodulatory role by stimulating or inhibiting the T-CELL activation process.
A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.
A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.
Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.
DNA sequences encoding the delta chain of the T-cell receptor. The delta-chain locus is located entirely within the alpha-chain locus.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.
Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Mice bearing mutant genes which are phenotypically expressed in the animals.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)
An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)
A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.
A condition consisting of inflammatory eye disease usually presenting as interstitial KERATITIS, vestibuloauditory dysfunction, and large- to medium-vessel vasculitis.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
The property of the T-CELL RECEPTOR which enables it to react with some antigens and not others. The specificity is derived from the structure of the receptor's variable region which has the ability to recognize certain antigens in conjunction with the MAJOR HISTOCOMPATIBILITY COMPLEX molecule.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Termination of pregnancy under conditions allowed under local laws. (POPLINE Thesaurus, 1991)
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A republic in western Africa, south of GUINEA and west of LIBERIA. Its capital is Freetown.
A contraceptive method whereby coitus is purposely interrupted in order to prevent EJACULATION of SEMEN into the VAGINA.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).
A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
DNA sequences encoding the gamma chain of the T-cell receptor. The human gamma-chain locus is organized similarly to the TcR beta-chain locus.
Reduction in the number of lymphocytes.
Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.
An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.
A costimulatory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 RECEPTOR. It is closely-related to CD274 antigen; however, its expression is restricted to DENDRITIC CELLS and activated MACROPHAGES.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
A family of receptors that modulate the activation of T-LYMPHOCYTES by the T-CELL ANTIGEN RECEPTOR. The receptors are responsive to one or more B7 ANTIGENS found on ANTIGEN-PRESENTING CELLS and, depending upon the specific ligand-receptor combination, modulate a variety of T-cell functions such as the rate of clonal expansion, CELL SURVIVAL and cytokine production. Although commonly referred to as costimulatory receptors, some of the receptors have inhibitory effects such as inducing PERIPHERAL TOLERANCE.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.
Cytokine that stimulates the proliferation of T-LYMPHOCYTES and shares biological activities with IL-2. IL-15 also can induce proliferation and differentiation of B-LYMPHOCYTES.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
An inhibitory T-lymphocyte receptor that has specificity for CD274 ANTIGEN and PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN. Signaling by the receptor limits T cell proliferation and INTERFERON GAMMA synthesis. The receptor also may play an essential role in the regulatory pathway that induces PERIPHERAL TOLERANCE.
Proteins prepared by recombinant DNA technology.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
A subclass of NK cell lectin-like receptors that includes both inhibitory and stimulatory members.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.
A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.
A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A specialized subset of T-LYMPHOCYTES that exhibit features of INNATE IMMUNITY similar to that of NATURAL KILLER CELLS. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D ANTIGEN.
A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.
Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.

Cell surface markers in HTLV-1 pathogenesis. (1/15)

 (+info)

T-cell activation and transplantation tolerance. (2/15)

 (+info)

Induced regulatory T cells: mechanisms of conversion and suppressive potential. (3/15)

 (+info)

Inhibitory receptors on lymphocytes: insights from infections. (4/15)

 (+info)

Multiple sclerosis. (5/15)

 (+info)

Positive and negative regulation of cellular immune responses in physiologic conditions and diseases. (6/15)

 (+info)

CD18 is required for optimal lymphopenia-induced proliferation of mouse T cells. (7/15)

 (+info)

TNF-induced target cell killing by CTL activated through cross-presentation. (8/15)

 (+info)

Background: The treatment of human cancer with monocyte-derived dendritic cells (MoDC) is a promising and innovative approach. However, many of the treated patients fail to respond to therapy. The reduced clinical antitumor response may be due to an inflammatory immune-suppressive tumor microenvironment. Regulatory T-cells (T-reg) and other cells with suppressive potential can promote an immune suppressive tumor microenvironment and thus play an important role in regulation of the immune response. Methods: Whole blood from n=100 cancer patients with various tumor types and from n=30 healthy donors were analysed by flow cytometry. CD4+ lymphocytes with immune suppressive potential were characterized by analysing the expression of CD25, CD39, CD127. Results: We found a significantly higher proportion of CD25+/CD39+ and of CD25+/CD127low T-helper cells in the blood of cancer patients as compared to healthy donors. This may indicate two different types of T-reg involved in immune suppression in ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
Deregulation of cell cycle control is the leading cause of cancer. The retinoblastoma (Rb) family members, including RB1/p105, RBL1/p107 and RBL2/p130, are crucial to restrain cell cycle progression and their inactivation, either direct or indirect, is a hallmark of most human tumors. In particular, RBL2/p130 emerging role in senescence and apoptosis, seems to contribute importantly to its tumor suppressor function. Furthermore, many studies largely contributed to establish RBL2/p130 as an important cancer target, which is inactivated by cell cycle kinases and whose deregulation underlies various cancer types. In this regard, we set out to restore RBL2/p130 function in tumors and exploit its tumor suppressive potential for cancer therapy. In particular, we have identified, through computational chemistry and molecular modeling studies, a small molecule able to act as a specific inhibitor of the CDK2-CycA complex and to reactivate the tumor suppressive function of RBL2/p130 in cancer.. We ...
There has been substantial interest in the subtypes of T cells involved in hypertension, and what they are doing to contribute to this disease. We found that mice lacking CD8+ T cells were protected from hypertension, whereas mice lacking CD4+ T cells or MHC class II were not. In this study, deep sequencing revealed an increase in V β chain clonality of CD8+ T cells in the kidney, but not in blood vessels or the spleen of hypertensive mice. Likewise, there was no clonal skewing of CD4+ T cells in any organ. We noticed that CD8−/− mice also displayed less vascular rarefaction and remodeling in the kidney as compared with WT or CD4−/− mice. An interesting study by Youn et al. (2013) compared circulating T cell phenotypes in newly diagnosed hypertensive patients to age- and sex-matched controls. They found that the number of circulating immunosenescent proinflammatory CD8+ T cells is increased in humans with hypertension. These cells produce increased amounts of IFN-γ, TNF-α, and the ...
Our data support that DRE is associated with an expansion of the CD4 Tcell subset in the peripheral blood and with a shift toward a proinflammatory Th17/Th1 CD4 Tcell immune profile. Our results further show that pathological levels of sNfL are more frequent in DRE, supporting a potential neurodegen …
The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naive cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naive T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naive cells, typical
Activation of CD4+ T cells occurs through the simultaneous engagement of the T-cell receptor and a co-stimulatory molecule (like CD28, or ICOS) on the T cell by the major histocompatibility complex (MHCII) peptide and co-stimulatory molecules on the APC. Both are required for production of an effective immune response; in the absence of co-stimulation, T cell receptor signalling alone results in anergy. The signalling pathways downstream from co-stimulatory molecules usually engages the PI3K pathway generating PIP3 at the plasma membrane and recruiting PH domain containing signaling molecules like PDK1 that are essential for the activation of PKCθ, and eventual IL-2 production. Optimal CD8+ T cell response relies on CD4+ signalling.[33] CD4+ cells are useful in the initial antigenic activation of naïve CD8 T cells, and sustaining memory CD8+ T cells in the aftermath of an acute infection. Therefore, activation of CD4+ T cells can be beneficial to the action of CD8+ T cells.[34][35][36] The ...
This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014 ...
We have confirmed and better defined the presence of a potentially important marker for malignant progression of BE. Furthermore, we have narrowed the area from 30 Mb, i.e., 7q33-q35 in our previous comparative genomic hybridization study (7) , to ∼2 Mb, i.e., the region between markers D7S2439 and D7S483. It implies the presence of a possible biomarker, which, in addition, has tumor suppressive activities. The 7q32.3-q36.1 region has not been reported frequently to be lost in human cancers. Thus far, it has been observed in gallbladder tumors, oral and oropharyngeal epithelial carcinomas, and leukemia (8, 9, 10) . In gallbladder tumors ,60% of allelic imbalance was seen for marker D7S798. Interestingly, it is located between D7S483 and D7S2465. We screened the critical area for known genes 7 with tumor suppressive potential and selected two possible candidates. Caspase 2 is known to stimulate apoptosis and is involved in shedding of intestinal epithelium (11) . Loss of these functions could ...
aim 2 will follow patients with rheumatoid arthritis longitudinally. Patients identified as having uncontrolled rheumatoid arthritis will undergo collection of endothelial cells by an iV placed in the antegrade position in the forearm followed by a thin wire inserted to collect the cells from the inner lining of the vein. The cells will processed and stained for markers of endothelial function and oxidative stress including enoS, phospho-enoS, nFkB, and nitrotyrosine using immunofluorescence technique. Flow mediated dilation (FMD) by ultrasound of the brachial artery on the contralateral arm will be used as an additional marker of endothelial function. a blood sample will be taken for analysis of inflammatory markers (eSR, CRP) and cytokine analysis (iL-1, iL-6, TnFa) by cytokine bead array. The patient will subsequently initiate the anti-TnF therapy prescribed by their treating rheumatologist. Four weeks following initiation of anti-TnF the procedures described above will be repeated.. ...
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. CD4+CD25+Foxp3+ regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3+ T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive
mice were protected from NEC and transfer of intestinal lymphocytes from NEC mice into naive mice induced intestinal inflammation. The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term human and mouse intestine, is required for lymphocyte influx through TLR4-mediated upregulation of CCR9/CCL25 signaling. TLR4 also mediates a STAT3-dependent polarization toward increased proinflammatory CD3+CD4+IL-17+ and reduced tolerogenic Foxp3+ Treg lymphocytes (Tregs). Th17 lymphocytes were required for NEC development, as inhibition of STAT3 or IL-17 receptor signaling attenuated NEC in mice, while IL-17 release impaired enterocyte tight junctions, increased enterocyte apoptosis, and reduced enterocyte proliferation, leading to NEC. Importantly, TLR4-dependent Th17 polarization could be reversed by the enteral administration of retinoic acid, which induced Tregs and decreased NEC severity. These findings identify an important role for ...
Activation of CD4+ T cells occurs through the simultaneous engagement of the T-cell receptor and a co-stimulatory molecule (like CD28, or ICOS) on the T cell by the major histocompatibility complex (MHCII) peptide and co-stimulatory molecules on the APC. Both are required for production of an effective immune response; in the absence of co-stimulation, T cell receptor signalling alone results in anergy. The signalling pathways downstream from co-stimulatory molecules usually engages the PI3K pathway generating PIP3 at the plasma membrane and recruiting PH domain containing signaling molecules like PDK1 that are essential for the activation of PKC-θ, and eventual IL-2 production. Optimal CD8+ T cell response relies on CD4+ signalling.[33] CD4+ cells are useful in the initial antigenic activation of naïve CD8 T cells, and sustaining memory CD8+ T cells in the aftermath of an acute infection. Therefore, activation of CD4+ T cells can be beneficial to the action of CD8+ T cells.[34][35][36] The ...
Activation of CD4+ T cells occurs through the simultaneous engagement of the T-cell receptor and a co-stimulatory molecule (like CD28, or ICOS) on the T cell by the major histocompatibility complex (MHCII) peptide and co-stimulatory molecules on the APC. Both are required for production of an effective immune response; in the absence of co-stimulation, T cell receptor signalling alone results in anergy. The signalling pathways downstream from co-stimulatory molecules usually engages the PI3K pathway generating PIP3 at the plasma membrane and recruiting PH domain containing signaling molecules like PDK1 that are essential for the activation of PKCθ, and eventual IL-2 production. Optimal CD8+ T cell response relies on CD4+ signalling.[33] CD4+ cells are useful in the initial antigenic activation of naïve CD8 T cells, and sustaining memory CD8+ T cells in the aftermath of an acute infection. Therefore, activation of CD4+ T cells can be beneficial to the action of CD8+ T cells.[34][35][36]. The ...
Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo.. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.. Journal of Medicinal Food, Volume: 7 Issue 1: July 7, 2004 ...
CD2 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor. It interacts with other adhesion molecules, such as lymphocyte function-associated antigen-3 (LFA-3/CD58) in humans, or CD48 in rodents, which are expressed on the surfaces of other cells. In addition to its adhesive properties, CD2 also acts as a co-stimulatory molecule on T and NK cells. CD2 is a specific marker for T cells and NK cells, and can therefore be used in immunohistochemistry to identify the presence of such cells in tissue sections. The great majority of T cell lymphomas and leukaemias also express CD2, making it possible to use the presence of the antigen to distinguish these conditions from B cell neoplasms. Due to its structural characteristics, CD2 is a member of the immunoglobulin superfamily; it possesses two immunoglobulin-like ...
The present study demonstrates an early lymphocyte infiltration during the development of IR in a mouse model of HFD-induced obesity. In addition, our data show a correlation of adipose tissue lymphocyte content with waist circumference in patients with type 2 diabetes, and suggest the presence of activated proinflammatory CD4-positive lymphocytes in human adipose tissue.. Previous work has mainly focused on the role of macrophages in adipose tissue inflammation. As such, MCP-1 (CCL2) is produced by adipocytes in parallel with increasing adiposity and mice lacking CCR2, an important receptor for MCP-1, exhibit less macrophage infiltration in adipose tissues as well as a reduction in inflammatory gene expression.3 Interestingly, these mice are partially protected from developing HFD-induced IR and the fact that the protective effect in these mice is incomplete, suggested that other cell types may also contribute to adipose tissue inflammation and IR. Early work has already indicated the presence ...
Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas
They do not express costimulatory molecules (CD28) and PD-1 receptor inhibitors on the surface, but they express the inhibitory ... T cells which recognize viral fragments in MHC class I complex on the surface of infected cells and destroy these cells. ... CD8+T cells form up to 50 % of all peripheral blood memory cells in HCV-positive elderly individuals. The same effect on the ... Memory T cell inflation phenomenon is the formation and maintenance of a large population of specific CD8+ T cells in reaction ...
Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. SIGLECs are typically ... 2002). "Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone". Nat. Cell Biol. 4 ... It is also reported to bind to Vascular adhesion protein 1 (VAP-1) and to the co-stimulatory molecule CD24 also known as HSA ( ... expressed on cells of the innate immune system, with the exception of the B-cell expressed SIGLEC6 (MIM 604405).[supplied by ...
Cell to cell contact: Type 1 regulatory T cells poses inhibitory receptor CTLA-4 through which they exert suppressor function. ... IL-10 indirectly downregulates MHC II molecules and co-stimulatory molecules on antigen-presenting cells (APC) and force them ... cells are a class of regulatory T cells participating in peripheral immunity as a subsets of CD4+ T cells . Tr1 cells regulate ... The suppressing and tolerance-inducing effect of Tr1 cells is mediated mainly by cytokines. The other mechanism as cell to cell ...
A balance among costimulatory and inhibitory signals is required for immune homeostasis. Excessive costimulation and/or ... natural killer cells, T and B cells) and the signalling properties of each receptor. All of the Fcγ receptors (FcγR) belong to ... The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and is called CD16 or ... These allergen-bound IgE molecules interact with Fcε receptors on the surface of mast cells. Activation of mast cells following ...
It depends on the balance of activating and inhibitory NK cell receptors and on their ligands expressed by the graft. Receptors ... T-lymphocytes must receive costimulatory signal. There are costimulatory molecules on T-cell surface and APCs express their ... KIR receptors provide inhibitory signal). So if these ligands are missing, there is no inhibitory signal and NK cell becomes ... there are also such receptors on T-lymphocytes that cause inhibition of T-cell activation (for instance CD152/CTLA-4 receptor ...
Costimulatory molecules in T-cell activation and transplantation: Section 2: The CD28 receptor family". In Burlingham WJ, ... Some cancer cells evade destruction by the immune system through an overexpression of B7 ligands that bind to inhibitory CD28 ... CD28 family receptors are a group of regulatory cell surface receptors expressed on immune cells. The CD28 family in turn is a ... CD28 receptors play a role in the development and proliferation of T cells. The CD28 receptors enhance signals from the T cell ...
KIR: short for Killer-cell Immunoglobulin-like Receptor, is a receptor for MHC Class I molecules on Natural Killer cells. ... B7-H3: also called CD276, was originally understood to be a co-stimulatory molecule but is now regarded as co-inhibitory. The ... Its ligand is ICOSL, expressed mainly on B cells and dendritic cells. The molecule seems to be important in T cell effector ... CD137-mediated signaling is also known to protect T cells, and in particular, CD8+ T cells from activation-induced cell death. ...
Fc receptors are found on many immune system cells, including NK cells. When NK cells encounter antibody-coated cells, the ... For example, anti-PD-1 drugs with Fc regions that bind inhibitory Fc receptors can have decreased therapeutic efficacy. Imaging ... Furthermore, antibodies targeting the co-stimulatory protein CD40 require engagement with selective Fc receptors for optimal ... Dendritic cell receptors such as TLR3, TLR7, TLR8 or CD40 have been used as antibody targets. Dendritic cell-NK cell interface ...
"Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by ... "Conservation of structural features reveals the existence of a large family of inhibitory cell surface receptors and ... "What controls T cell receptor phosphorylation?". Cell. 142 (5): 668-9. doi:10.1016/j.cell.2010.08.018. PMID 20813251. Davis SJ ... A prominent member of this receptor family is the T-cell receptor. Members of the Non-catalytic tyrosine-phosphorylated ...
... lymphocyte must engage both antigen and costimulatory ligand on the same antigen-presenting cell. T cell receptor (TCR) ... CD86 and CD80 bind as ligands to costimulatory molecule CD28 on the surface of all naïve T cells, and to the inhibitory ... B-cells (including memory B-cells), and on other antigen-presenting cells. Along with CD80, CD86 provides costimulatory signals ... dendritic cells, and even activated B-cells. They can also be induced on other cell types, for example T cells. CD86 expression ...
Allison's research is in molecular immunology of the T-cell antigen receptor complex, co-stimulatory receptors, and other ... In 1996, Allison was the first to show that antibody blockade of a T-cell inhibitory molecule (known as CTLA-4) could lead to ... In 1982, Allison first discovered the T-cell receptor. Allison's research to elucidate mechanisms of T-cell responses was ... This concept of blocking T-cell inhibitory pathways as a way of unleashing anti-tumor immune responses and eliciting clinical ...
Coggeshall KM (June 1998). "Inhibitory signaling by B cell Fc gamma RIIb". Current Opinion in Immunology. 10 (3): 306-12. doi: ... a key subset for the generation of autoantibody producing autoreactive plasma B cells.[59] A balance among costimulatory and ... On NK cellsEdit. The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and ... Langerhans cells Phagocytosis. Degranulation (eosinophils) FcγRIIB1 (CD32) IgG Low (Kd , 10−7 M) B Cells. Mast cells No ...
... and contributes to their inhibitory function. T cell activation through the T cell receptor and CD28 leads to increased ... CTLA4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and ... CTLA4 transmits an inhibitory signal to T cells, whereas CD28 transmits a stimulatory signal. CTLA4 is also found in regulatory ... and have low CTLA4 protein expression in T regulatory cells, hyperactivation of effector T cells, low switched memory B cells, ...
... B is an inhibitory surface receptor that is part of a large population of B cell co-receptors, which act to modulate ... On DCs, CD32A plays an important role in maturation and the upregulation of costimulatory molecules on the cell surface, ... Activated CD32B has the ability to cross-link with B cell receptors (BCRs), which increases the threshold for B cell activation ... July 2007). "Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the ...
In these cells, a small amount of LYN is associated with cell surface receptor proteins, including the B cell antigen receptor ... Biochemical analysis of cells from these mutants revealed that Lyn is essential in establishing ITIM-dependent inhibitory ... These mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory ... attenuate cell activation and can mediate tolerance. In B cells, Lyn sets the threshold of cell signaling and maintains the ...
"BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1". Nature Immunology. 4 (7): 670-9. doi:10.1038/ ... "Expression of the novel co-stimulatory molecule B7-H4 by renal tubular epithelial cells". Kidney International. 70 (12): 2092-9 ... V-set domain-containing T-cell activation inhibitor 1 is a protein that in humans is encoded by the VTCN1 gene. B7H4 belongs to ... These proteins are expressed on the surface of antigen-presenting cells and interact with ligands (e.g., CD28; MIM 186760) on T ...
... binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition ... The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with ... "Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target". ... PD-L1 is expressed on T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells. ...
... binding to the same receptors to prime T cells. CD80 can be found on the surface of various immune cells including B cells, ... Chambers BJ, Salcedo M, Ljunggren HG (October 1996). "Triggering of natural killer cells by the costimulatory molecule CD80 (B7 ... In contrast to the stimulatory interaction with CD28, CD80 also regulates the immune system through an inhibitory interaction ... B-cells, dendritic cells and T-cells that result in T and B-cell activation, proliferation and differentiation. CD80 is an ...
Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab. ITGAL gene encodes ... Yusuf-Makagiansar H, Makagiansar IT, Hu Y, Siahaan TJ (Dec 2001). "Synergistic inhibitory activity of alpha- and beta-LFA-1 ... "Differentially regulated cell surface expression of leukocyte adhesion receptors on neutrophils". Kidney Int. 40 (5): 899-905. ...
"A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing". ... "Costimulatory Molecules on Immunogenic Versus Tolerogenic Human Dendritic Cells". Frontiers in Immunology. 4: 82. doi:10.3389/ ... "Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell ... These tolerogenic effects are mostly mediated through regulation of T cells such as inducing T cell anergy, T cell apoptosis ...
... been shown to enhance CD8+ T cell secretion of the cytotoxic molecules Granzyme B and Perforin and potentiate T cell receptor ... It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also ... Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In ... mast cells, CD4+CD25+Foxp3+ regulatory T cells, and in a certain subset of activated T cells and B cells. IL-10 can be produced ...
... signaling through CD28 in mouse T cells can act to some extent as a substitute activating signal for T-cell receptor signaling ... Thy-1 has been suggested to interact with G inhibitory proteins, the Src family kinase (SFK) member c-fyn, and tubulin within ... Crosslinking Thy-1 molecules in the membrane raft, in the context of strong costimulatory ... Thy 1 is also a marker of other kind of stem cells, for example: mesenchymal stem cells, hepatic stem cells ("oval cells"), ...
... costimulatory receptor) for the MHC-II binding with TCR and CD4. CD28 increases the IL-2 secretion from the T-cells if it is ... The mAb causes the release of HIV-1-inhibitory b-chemokines, preventing other cells from becoming infected. Cancer-based ... A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to ... These categories of cell surface receptors are prominently referred to as co-receptors. Co-receptors are also referred to as ...
May 2006). "No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell ... April 2001). "B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells". The Journal of ... PD-L2 is one of two known ligands for Programmed cell death protein 1 (PD-1). PD-L2 is a cell surface receptor belonging to the ... April 2001). "B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells". The Journal of ...
"PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells". EMBO Molecular Medicine. 3 ... "Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses". Immunity ... Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an ... PD-L1 on the cell surface binds to PD-1 on an immune cell surface, which inhibits immune cell activity. Among PD-L1 functions ...
However, along with the antigens, the dendritic cells present an inhibitory signal. That signal binds to a receptor, cytotoxic ... CD28 at that time was a recently identified "T cell costimulatory" molecule important for T cell activation. Anti-CTLA-4 ... Ipilimumab turns off this inhibitory mechanism and allows the lymphocytes to continue to destroy cancer cells. Cancer cells ... Ipilimumab binds to CTLA-4, blocking the inhibitory signal, which allows the CTLs to destroy the cancer cells. In 2014 a study ...
... a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells". Journal of ... "Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated ... Growth hormone receptor, HoxA10, Insulin receptor, Insulin-like growth factor 1 receptor, IRS1, Janus kinase 1, Janus kinase 2 ... Feng GS (2007). "Shp2-mediated molecular signaling in control of embryonic stem cell self-renewal and differentiation". Cell ...
"Entrez Gene: TREML1 triggering receptor expressed on myeloid cells-like 1". Strausberg RL, Feingold EA, Grouse LH, et al. (2003 ... a putative inhibitory receptor within the TREM cluster". Blood. 100 (10): 3822-4. doi:10.1182/blood-2002-02-0523. PMID 12393607 ... a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than ... 2006). "The structure of the extracellular domain of triggering receptor expressed on myeloid cells like transcript-1 and ...
... which has co-stimulatory role in B and T cells. CD200 (OX-2) is a type 1 membrane glycoprotein, which delivers an inhibitory ... The cell surface receptor interleukin-3 receptor-alpha (CD123) is overexpressed on CD34+CD38- leukemic stem cells (LSCs) in ... IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells". Cell Stem Cell. 5 (1): 31-42. doi:10.1016/j. ... "Critical appraisal of the side population assay in stem cell and cancer stem cell research". Cell Stem Cell. 8 (2): 136-47. doi ...
... by killer inhibitory and killer activatory receptor on NK cells and by various receptors on other cells including Fc receptor ... affinity T cell down-modulation of costimulatory molecules on dendritic cells mediated by T cells leads to regulation of T cell ... On T cells and B cells, trogocytosis is triggered when the T cell receptor (TCR) on T cells or B cell receptor (BCR) on B cells ... Epratuzumab (a CD22 Mab) acts using trogocytosis to transfer CD22 and other B-cell proteins from B cells to effector cells. ...
When a T-cell receptor is activated by contact with a peptide:MHC complex, CD45 dephosphorylates inhibitory tyrosine of ... T cell are less dependent on costimulatory signals and higher antigen concentration than naive T cell.[16] ... T cells expressing this receptor are referred to as α:β (or αβ) T cells, though a minority of T cells express an alternate ... The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes,[1] that is responsible for ...
Both CD80 and CD86 activate the CD28 receptor. These proteins are also known as co-stimulatory molecules. ... Both cytokines are inhibitory to helper T cells; TGF-β suppresses the activity of most of the immune system. There is evidence ... Their main effector cells are NK cells as well as CD8 T cells, IgG B cells, and IL-10 CD4 T cells. The key THαβ transcription ... Like all T cells, they express the T cell receptor-CD3 complex. The T cell receptor (TCR) consists of both constant and ...
The only co-stimulatory receptor expressed constitutively by naïve T cells is CD28, so co-stimulation for these cells comes ... Exhausted T cells typically indicate higher levels of CD43, CD69 and inhibitory receptors combined with lower expression of ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... cells. A T cell becomes a CD4+ cell by down-regulating expression of its CD8 cell surface receptors. If the cell does not lose ...
... acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells (T ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... Leukemia/leukocyte inhibitory factor (LIF). *Oncostatin M (OSM). *Thymic stromal lymphopoietin (TSLP) ... B cells[edit]. T cell-dependent B cell activation, showing a TH2-cell (left), B cell (right), and several interaction molecules ...
The only co-stimulatory receptor expressed constitutively by naïve T cells is CD28, so co-stimulation for these cells comes ... Exhausted T cells typically indicate higher levels of CD43, CD69 and inhibitory receptors combined with lower expression of ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... such as B cells and natural killer cells, by the presence of a T-cell receptor on the cell surface. They are called T cells ...
The P2RX7 receptor is overexpressed in most malignant tumors. The expression of the adenosine A2A receptor on endothelial cells ... As a result, the expression of co-stimulatory molecules by APCs is upregulated. The inhibition of the P2X7 receptor increases ... Martinson J, Muren A (1963). "Excitatory and inhibitory effects if vagus stimulation on gastric motility in the cat". Acta ... It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions. ...
Schmitz ML, Krappmann D (2006). "Controlling NF-kappaB activation in T cells by costimulatory receptors". Cell Death Differ. 13 ... "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature. 397 (6717): 363-8. Bibcode ... Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID ... Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M regulation". Cell Res. 15 (3): 143-9. doi:10.1038/sj.cr.7290279 ...
... which disrupts T cell costimulatory pathways and PD-L1, which activates T cell inhibitory pathway. See also: US 20130058900 ... "Small Molecule-Mediated TGF-β Type II Receptor Degradation Promotes Cardiomyogenesis in Embryonic Stem Cells". Cell Stem Cell. ... human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells". Gene ... "Human Somatic Cell Nuclear Transfer Using Adult Cells". Cell Stem Cell. 14 (6): 777-780. doi:10.1016/j.stem.2014.03.015. PMID ...
Antitumor receptors genetically engineered into normal T cells can be used for therapy. T cells can be redirected by the ... antibodies bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses, known as ... potentially including costimulatory domains encoding CD28 or CD137. CARs can provide recognition of cell surface components not ... CD4+ T cells can also promote tumor rejection. CD4+ T cells enhance CD8+ T cell function and can directly destroy tumor cells. ...
On T cells, membrane-anchored LAG-3 is an inhibitory receptor downregulating T-cell receptor (TCR) signaling. Efti - as a ... And there was an increase in the expression of co-stimulatory molecules CD27 and CD28 (CD27+CD28+, p=0.016; and CD27-CD28+, p= ... Activated T cells. The eight patients experienced sustained CD8+ T-cell activation (as measured by percentage of CD8+ T cells ... Increase in relevant cell numbers. There was a sustained increase in the number of monocytes, NK cells, and activated CD8+ T ...
"Killer cell activating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in rheumatoid ... This inhibitory effect of Kv1.3 blockers is partial and stimulation strength dependent, with reduced inhibitory efficacy on T ... When naïve T cells and central memory T cells (TCM) are activated they upregulate KCa3.1 expression to ~500 per cell without ... and cell proliferation. Effector memory T cells that are CD28+ are refractory to suppression by Kv1.3 blockers when they are co ...
"SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. 273 (42): 27518-27523. doi ... a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". J. Immunol. 164 ( ... SLP-76 might serve as an integration point for signals by activating NK cell receptors. In NK cells, SLP-76 can be ... "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. 273 (42): 27518-27523. doi ...
... a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". Journal of ... Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D (April 2002). "NMDA receptor function is regulated by the inhibitory ... Cell. 159 (5): 1086-1095. doi:10.1016/j.cell.2014.10.041. PMC 4243054. PMID 25416947. Ikeuchi K, Inada T (June 2016). "Ribosome ... "The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts". The Journal of ...
... and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and costimulatory receptors. ... and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and costimulatory receptors. ... NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors ... NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors ...
Better Cell-Based Assays to Measure Co-Inhibitory and Co-Stimulatory Receptors in the Development of Therapeutic Antibodies. ... Cell Biology Cell Health Cell Line + Sample Identification Cell Signaling Energy Metabolism Imaging + Immunological Detection ... Co-stimulatory receptors: GITR, CD40, OX40, 4-1BB. Current approaches to measure the potency of immunotherapy drugs include in ... Somberg worked at Life Technologies where he led product development and service efforts in biochemical and cell-based assays ...
CD226 recognizes CD155 and CD112, which are also ligands for the inhibitory receptors TIGIT and CD96. One of the concerns in ... T cells, and several types of myeloid cells. At early time points of T cell activation by pervanadate, the costimulatory ... VAV1, a T cell hub. The guanine nucleotide exchange factor VAV1 is required for T cell receptor (TCR) signaling and activation ... Human cell lines and primary CD4+ T cells. The Jurkat E6.1 T cell line and its CD226-overexpressing variant were provided by R ...
ICOS is a CD28-like costimulatory receptor with a unique B7-like ligand. PD-1 is an inhibitory receptor, with two B7-like ... T cell activation is dependent upon signals delivered through the antigen-specific T cell receptor and accessory receptors on ... Integration of signals through this family of costimulatory and inhibitory receptors and their ligands is critical for ... the T cell. A primary costimulatory signal is delivered through the CD28 receptor after engagement of its ligands, B7-1 (CD80) ...
Conditioning of antigen-specific T-cells by activated and antigen-pulsed MSCs prevented T-cells to proliferate upon subsequent ... Conditioning of antigen-specific T-cells by activated and antigen-pulsed MSCs prevented T-cells to proliferate upon subsequent ... In sum, activation of MSCs with inflammatory stimuli turns these cells into suppressive cells, capable of mediating adaptive ... In sum, activation of MSCs with inflammatory stimuli turns these cells into suppressive cells, capable of med... ...
First, TIGIT is an inhibitory counterpart of the co-stimulatory receptor CD226. When TIGIT is present on the surface of ... Highest expression levels are observed on effector CD4+ and CD8+ T cells, regulatory T cells, and NK cells. TIGIT has several ... The assay consists of two genetically engineered cell lines:. TIGIT Effector Cells: Jurkat T cells expressing human TIGIT with ... The bioassay consists of two genetically engineered cell lines, TIGIT Effector Cells and CD155 aAPC/CHO-K1 Cells. Panel A. When ...
However, newer treatments have shifted attention to targets on immune cells, resulting in dramatic responses. The effect of DNA ... Historically the development of anticancer treatments has been focused on their effect on tumor cells alone. ... Costimulatory receptor agonists or antagonists of inhibitory signals augment antigen-specific T-cell responses [133]. ... PD-1 is a transmembrane inhibitory coreceptor. Expression of PD-1 on T-cells and PD-L1 ligand interaction has been shown to ...
Negative feedback of T cell activation through inhibitory adapters and costimulatory receptors. Immunol. Rev. 192:143. ... converts CTLA-4 from an inhibitory receptor into an activating receptor for T cells. Because the T cell response to 24:26 ... Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J. Exp. Med. 160:1284. ... by which a bispecific tandem ScFv ligand of CTLA-4 converts this inhibitory receptor on T cells into an activating receptor. ...
Co-Stimulatory and Co-Inhibitory Receptor-Ligand Pairs. Vincenzo Cerundolo, University of Oxford, UK Harnessing NKT cells in ... Adoptive cell transfer (ACT) of anti-tumor T cells after the depletion host immune cells causes objective regression in about ... Exploiting T Cell Receptor Genes for Cancer Immunotherapy. Michel Sadelain, Memorial Sloan Kettering Cancer Center, USA Novel ... Potentials of T Cell Homeostatic Cytokines. Yang Liu, University of Michigan, Ann Arbor, USA Short Talk: CD24 Controls T Cell ...
Costimulatory and Inhibitory T-Cell Receptors * Programmed Cell Death 1 Receptor Grant support * 2U54 CA151819/CA/NCI NIH HHS/ ... There are several other checkpoint molecules that are likely potential inhibitory targets. The outcome of blocking some of ... Programmed Cell Death 1 Receptor / antagonists & inhibitors* * Programmed Cell Death 1 Receptor / metabolism ...
The diversity of costimulatory and inhibitory receptor pathways and the regulation of antiviral T cell responses. Curr Opin ... we wondered whether these cells expressed the inhibitory receptor PD-1, a marker of impaired T cells. In naive mice, less than ... Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1 ... Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells ...
Immune cell function implicates important modulators known as cosignaling receptors. On T cells, the cosignaling receptors ... The CD28 immunoglobulin-superfamily is composed of coinhibitory and costimulatory receptors. Programmed Death-1 (PD-1) is one ... It contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. It is encoded by the PDCD1 gene, ... The PD1.3 monoclonal antibody recognizes T cells, activated CD4 and CD8 positive cells and activated B cells. This antibody has ...
The NK cell-mediated killing is controlled by inhibitory, costimulatory, and lysis receptors (2). The main lysis receptors ... The killing of .221/Cw4-infected cells is influenced by the balance between inhibitory and activating receptors. The NK cells ... The NK cell cytotoxic activity is regulated by both inhibitory and activating NK receptors. Thus, changes in the expression ... The activity of NK cells is balanced by inhibitory and killing receptors (2), and killing will occur only if the killing ...
... and co-stimulatory or co-inhibitory signals.. The potential role of inhibitory receptors in the treatment of psoriasis ... B cells require a co-stimulatory signal together with antigen recognition for B cell activation.. Negative regulation of B cell ... The balance of co-stimulatory and co-inhibitory molecules, which are expressed on T-cells control the immunological response, ... Engagement of T cells requires two signals: antigen recognition through the T cell receptor (TCR) and major histocompatibility ...
Expression of costimulatory and inhibitory receptors in FoxP3+ regulatory T cells within the tumor microenvironment: ... Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001. Review. ... Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells. ... Dynamic Imprinting of the Treg Cell-Specific Epigenetic Signature in Developing Thymic Regulatory T Cells. ...
However, these agents typically function by activating costimulatory receptors (e.g., Ox40, Glucocorticoid induced TNF receptor ... which block key inhibitory pathways involved in T cell activation, have shown significant clinical potential in a number of ... No significant differences were observed for CD45+ cells, CD103+ DCs, total CD11c+ DCs, CD8+ T cells, CD4+ T cells, or NK cells ... Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 31, ...
The human immune system is regulated by a broad network of co-inhibitory and co-stimulatory receptors that control the type, ... Quantitative cell-based assays for characterization of antibodies targeting co-stimulatory immune checkpoint receptors [ ... Quantitative cell-based assays for characterization of antibodies targeting co-stimulatory immune checkpoint receptors. Julia K ... Quantitative cell-based assays for characterization of antibodies targeting co-stimulatory immune checkpoint receptors ...
Human T Cell Co-inhibitory and Co-stimulatory Receptor IHC Antibody Sampler Kit#44689. Citations (1) ... and some B cell malignancies including hairy cell leukemia (10,11). CD19 is a co-receptor expressed on B cells that amplifies ... Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.. D2W8E is a trademark of Cell Signaling Technology ... but has also been described on a subset of dendritic cells in mice (2,3). On T cells, CD8 is a co-receptor for the TCR, and ...
... which inhibit T cell activation. This is the case of the T cell inhibitory receptor PD-1 ligand, PD-L1 [74-78]. PD-L2 is a ... tolerogenic DCs upregulate the surface expression of inhibitory costimulatory molecules, ... "Tumor cells convert immature myeloid dendritic cells into TGF-β-secreting cells inducing CD4+CD25+ regulatory T cell ... These T cells exert their cytotoxic activities towards transgene-expressing cells. Therefore, to avoid T cell responses, the ...
The immune system is tightly controlled by co-stimulatory and co-inhibitory ligands and receptors. These molecules provide not ... T cell subsets (see total CD4+ T cells or Foxp3− naive T cells and Foxp3+ nTreg cells and memory CD4+ T cells), whereas CD8+ T ... ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature. 409:97-101. doi:10.1038/35051100. ... of cells were apoptotic in the presence of control-Ig. Similarly, of the cells within the live cell R1 gate, ∼72.6% cells ...
TILs express a wide range of co-inhibitory and co-stimulatory receptors. (A and B) Gene expression profile of cell surface ... which revealed expression of a broad panel of both inhibitory receptors and co-stimulatory receptors. These approaches have ... Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10:29-37. ... Moreover, the additional co-stimulatory and co-inhibitory receptors identified in our current work could represent functionally ...
... chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together ... expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific ... As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic ... The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3−. ...
Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci U S A. ... Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key inhibitory receptor that affects T cell function and plays a critical role ... CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543-9553.. View this ... T cell activation is initiated when antigen is presented to the T cell receptor (TCR) complex by MHC class I or II on an ...
Signal Transduction Via Co-stimulatory and Co-inhibitory Receptors. Pages 85-133 ... Co-signal Molecules in T Cell Activation will be a valuable reference guide to co-stimulation for basic and clinical ... Co-signal Molecules in T Cell Activation. Book Subtitle. Immune Regulation in Health and Disease. Editors. * Miyuki Azuma ... Co-signal Molecules in T Cell Activation. Immune Regulation in Health and Disease. Editors: Azuma, Miyuki, Yagita, Hideo (Eds ...
Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of ... 3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to ... Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of ... We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The ...
Cell surface-attached costimulatory members of the TNF and TNFR superfamilies. Schematic receptor-ligand pair interactions of ... Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its ... such as T-cell antigen receptor (TCR) ligation on T cells or on recognition of antibody-coated target cells sensed by FcRγIII ( ... Expression of CD137 is also found on activated B cells, dendritic cells, myeloid precursors, mast cells, and endothelial cells ...
Cell surface-attached costimulatory members of the TNF and TNFR superfamilies. Schematic receptor-ligand pair interactions of ... Plus (+), minus (−), and question mark (?) signs placed at the side of the arrows indicate activatory and inhibitory signals or ... This death domain recruits apoptosis inducing molecules upon ligation of the receptor and is absent from the costimulatory ... CD137 expression on dendritic cells, activated CD4 T cells (including Tregs), and on tumor blood and lymphatic vessels could ...
"NK cell receptor-bacterial interactome". We will examine the hypothesis that NK inhibitory and activating receptors are ... 3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to ... "NK cell receptor-bacterial interactome". We will examine the hypothesis that NK inhibitory and activating receptors are ... 2) New cytokines and cell surface receptors that are expressed in DCs and signal to T cells. (3) New key regulators in DC ...
Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer ... PBMCs (effector cell) and K562 cells (targeted cell; 2 x 104 cells/well) were seeded in the well in a ratio of 1.25:1 and ... Bhat R, Rommelaere J. NK-cell-dependent killing of colon carcinoma cells is mediated by natural cytotoxicity receptors (NCRs) ... Natural killer cell cytotoxicity before and after surgery NK cell, natural killer cell; Propofol-ketorolac group, propofol- ...
Co-stimulatory and co-inhibitory receptors are crucial to determine functional outcomes upon activation. We found an imbalance ... CD4+ Regulatory T cells (Tregs) are crucial to maintain tolerance, balancing effector T cell responses to harmful agents and ... Her work focuses on the role of co-stimulatory and co-inhibitory receptors in primary human Treg function in health and disease ... receptor-receptor and receptor-ligand interactions and study their role in primary human Treg function in health and disease. ...
  • In response to sensing the danger signals by PRRs such as toll-like receptors, APCs produce co-stimulatory molecules and polarizing cytokines that promote adaptive immunity into the best responses against the danger signals. (thefreedictionary.com)
  • The balance of co-stimulatory and co-inhibitory molecules, which are expressed on T-cells control the immunological response, is crucial in the adaptive immunosuppression induced by sepsis. (thefreedictionary.com)
  • MHC associated antigen presentation and interaction of co-stimulatory molecules particularly T-cell surface specific glycoprotein CD28 with T-cell activation antigens CD80 and CD86 that are expressed on antigen presenting cells15. (thefreedictionary.com)
  • The acquisition gives Bristol-Myers Squibb full rights to Cormorant's HuMax-IL8 antibody programme and the lead candidate HuMax-IL8, a Phase 1/2 monoclonal antibody targeted against interleukin-8 that represents a potentially complementary immuno-oncology mechanism of action to T-cell directed antibodies and co-stimulatory molecules. (thefreedictionary.com)
  • The capacity to engineer mAbs against cell surface receptors has renewed the interest in the development of these molecules as biopharmaceuticals ( 13 ). (jimmunol.org)
  • There are several other checkpoint molecules that are likely potential inhibitory targets. (nih.gov)
  • Binding of CD28 on the T cell to B7-1 (CD80) and B7-2 (CD86) molecules on the antigen-presenting cell creates an amplifying signal required for full T cell activation. (jci.org)
  • Fc receptor-mediated opsonization also enhances expression of costimulatory molecules such as CD40, B7-1 (CD80), and B7-2 (CD86) on the DC surface, promoting T cell activation. (nih.gov)
  • delivery of potent immunosuppressive cytokines and other molecules, modification of intracellular signalling pathways in dendritic cells, and de-targeting transgene expression from dendritic cells using microRNA technology. (hindawi.com)
  • These molecules provide not only a second signal for T cell activation but also a balanced network of positive and negative signals to maximize immune responses against infection while limiting immunity to self. (rupress.org)
  • The first part of the book is devoted to co-signal molecules and the regulation of T cells. (springer.com)
  • Following an initial overview, subsequent chapters examine each co-signal molecule in turn and discuss the mechanisms by which co-signal molecules regulate the different types of T cell. (springer.com)
  • Co-signal Molecules in T Cell Activation will be a valuable reference guide to co-stimulation for basic and clinical researchers in the fields of both immunology and pharmaceutical science. (springer.com)
  • They do not express costimulatory molecules (CD28) and PD-1 receptor inhibitors on the surface, but they express the inhibitory molecules KLRG1 and CD85. (wikipedia.org)
  • Costimulatory molecules will subsequently determine the outcome of the primary antigen recognition by providing signals that will amplify, complement, and modulate those elicited from the TCR or CD16. (aacrjournals.org)
  • Four families of molecules play important roles in immune synapses: the immunoglobulin superfamily, the integrin superfamily, C-type lectins, and the TNF/TNF receptor (TNFR) families. (aacrjournals.org)
  • Receptors are color-coded for activation-dependent inducibility and the family of molecules is shape-coded. (aacrjournals.org)
  • It is well known that some of the TNF members act as cell surface-attached molecules and some as soluble cytokines that in some cases can heterotrimerize. (aacrjournals.org)
  • This death domain recruits apoptosis inducing molecules upon ligation of the receptor and is absent from the costimulatory members whose main function is to convey proinflamatory and activatory signals. (aacrjournals.org)
  • Our group also discovered the B7-1 and B7-2 molecules that bind to the costimulatory CD28 and coinhibitory CTLA-4 receptor and provide the critical costimulatory signal for full T cell activation, clonal expansion, and development of effector function through their interaction with CD28 on T cells. (dana-farber.org)
  • In addition, NLF CD56dim cells expressed lower levels of cytotoxicity-associated genes, perforin (PRF1) and granzyme B (GZMB), and increased levels of cytokines and cell signaling molecules, TRAIL, IFNGR2, and IL8, as compared to PB CD56dim cells. (deepdyve.com)
  • Plasma, in the presence of an FcγRIIb blockade, caused the DCs to up-regulate the expression of costimulatory molecules and to produce the inflammatory mediator IL-12p70. (pnas.org)
  • The both B7 molecules are expressed on professional antigen-presenting cells and are essential for T cell activation, the both molecules can also substitute for each other in this process. (fishersci.com)
  • The interaction between the T-cell receptor complex (TCR) and antigenic peptides bound in surface MHC molecules provides the specificity that defines adaptive T-cell immunity. (pnas.org)
  • In addition to TCR activation, costimulation via ligation of the coreceptor CD28 on T cells by B7 molecules on antigen-presenting cells (APCs) is required for optimal T-cell activation ( 1 ). (pnas.org)
  • Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is rapidly up-regulated following T-cell activation and binds to B7 molecules with a higher affinity than does CD28. (pnas.org)
  • In addition, tumors themselves sometimes express PD-L1, which can negatively signal T cells through both the PD-1 and B7-1 molecules on their surface ( 5 ). (pnas.org)
  • Although CTLA-4 and PD-1 belong to the same family of molecules and are both coinhibitory, evidence suggests they use distinct nonredundant mechanisms to inhibit T-cell activation. (pnas.org)
  • The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. (aspetjournals.org)
  • Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. (aspetjournals.org)
  • Also, sharing an immune cell lineage, malignant hematologic cells often express immune checkpoint molecules that are absent in solid tumor cells, thereby offering direct targets for immune checkpoint inhibition. (aspetjournals.org)
  • Targeting immune checkpoint molecules on the surface of tumor cells or immune cells has proven to be a highly effective approach in cancer immunotherapy. (aspetjournals.org)
  • While the impact of co-stimulatory molecules has been addressed in various studies, the role of co-inhibitory receptors has not been tested. (uni-muenchen.de)
  • Stimulation of TCR is triggered by MHC (Major Histocompatibility Complex) molecules on antigen presenting cells that present antigen peptides to TCR complexes and induce a series of intracellular signaling cascades that regulate T-cell development, homeostasis, activation, acquisition of effector's functions and apoptosis. (thermofisher.com)
  • Costimulation involves an integration of activating signals and inhibitory signals from CD28 and CTLA4 (Cytotoxic T-Lymphocyte Antigen-4) molecules, respectively, with TCR signals to determine the outcome of a T-cell's encounter with an antigen (Ref. 2). (thermofisher.com)
  • CTLA4 (CD152) is a member of a class of cell surface molecules capable of terminating early events in the receptor-mediated signaling cascade. (thermofisher.com)
  • T cell exhaustion is a state of cellular hyporesponsiveness that occurs in response to continued antigen stimulation or inflammation, wherein T cells produce fewer cytokines and cytotoxic molecules, lower expression levels of activating receptors, and increased expression levels of inhibitory receptors ( 1 ). (asm.org)
  • The NK regulatory mechanisms include the acquisition of MHC class II and costimulatory molecules to sub-optimal levels in order to induce T cell anergy. (bmj.com)
  • Objectives We aim to study the NKR and costimulatory molecules expression in NK cells from SLE patients, as well as its inhibitory function. (bmj.com)
  • Furthermore, we observed that the expression of the costimulatory molecules CD80, CD86 and CD134, as well as HLA-DR was increased in SLE patients compared to healthy controls. (bmj.com)
  • Conclusions Our results suggest that NK cells from SLE patients show an activating phenotype, which, in addition to the high expression of HLA-DR and costimulatory molecules provides them with the ability to present antigens and activate T cells. (bmj.com)
  • This property allows FcγRI to bind a sole IgG molecule (or monomer ), but all Fcγ receptors must bind multiple IgG molecules within an immune complex to be activated. (wikipedia.org)
  • Indeed, in contrast to conventional T cells that express a very diverse T cell receptor (TCR) repertoire and are restricted by polymorphic MHC molecules, innate like T cells display semi-invariant TCRs and are restricted by non-polymorphic MHC-Ib molecules. (prolekare.cz)
  • The most successful strategies for cancer immunotherapy have focused on targeting the T cell co-stimulatory and co-inhibitory molecules that regulate T cell activation. (rndsystems.com)
  • Scientists at R&D Systems are contributing to the effort to identify receptors for these molecules with the hope of developing reagents that will allow researchers to target these pathways and determine whether they have immunotherapeutic potential. (rndsystems.com)
  • We are interested in the contribution of cell surface molecules (positive and negative costimulatory molecules) on human T cells and antigen-presenting cells (APC) in immune responses. (meduniwien.ac.at)
  • a) A successful T-cell/DC interaction results in the organization of signaling molecules into an immune synapse. (brainscape.com)
  • Although the aetiology is unknown, several observations make currently clear that CD4 T cells play a key role in the pathogenesis: (1) RA associates with certain polymorphisms of HLA class II molecules, and (2) the repertoire and aging of CD4 T cells as well as the intracellular signalling mediating CD4 T cell activation are altered in RA patients. (intechopen.com)
  • These cells are under the regulatory control of nonconventional costimulatory molecules, display potent effector functions, and appear to be critical in the synovial and extra-articular manifestations of RA. (biomedcentral.com)
  • To gain a better understanding of this process the expression by these cells of cell surface activation markers, co-stimulatory molecules, and adhesion molecules was analysed. (bmj.com)
  • 4 5 Parameters affecting the ability of alveolar macrophages to present antigen to T cells include expression of co-stimulatory molecules such as CD80 and CD86 interacting with CD28 on T cells. (bmj.com)
  • The purpose of this study was to examine the phenotype of different cell populations in peripheral blood and bronchoalveolar lavage (BAL) fluid of patients with sarcoidosis, with the focus on activation markers, adhesion molecules, and co-stimulatory molecules. (bmj.com)
  • The signalling lymphocyte-activation molecules (SLAM) family of receptors encompasses a number of adhesion molecules expressed on the surface of leukocytes that play critical roles in both innate and adaptive immunity. (prolekare.cz)
  • As a consequence, CMV has evolved diverse countermeasures to avoid recognition by T cells, allowing it to interfere with the surface expression of major histocompatibility complex class I (MHC class I) and class II and costimulatory molecules, compromising antigen presentation [3] - [6] . (prolekare.cz)
  • The signalling lymphocyte-activation molecules (SLAM) family of cell-surface receptors is a distinct structural subgroup of the immunoglobulin (Ig) superfamily differentially expressed on hematopoietic cells and found to play pivotal roles in both innate and adaptive immunity [11] - [13] . (prolekare.cz)
  • Schematic of major costimulatory molecules belonging to the CD28 and TNF/TNFR (tumor necrosis factor receptor) superfamilies. (blackwaterpaddleandpedal.com)
  • The importance of B7-H molecules for the T cell/tumor communication and its impact on renal cell carcinoma (RCC) progression and prognosis has been recently described. (biomedcentral.com)
  • The constitutive and/or cytokine-induced expression of cytokine receptors signaling components and B7-H molecules in RCC cells were analysed by qPCR and flow cytometry. (biomedcentral.com)
  • Treatment of RCC cells with TNFα and IL-4 was accompanied by an activation of signaling molecules like NF-κB, IκB and STAT6. (biomedcentral.com)
  • B7 molecules are a growing protein family with diverse functions on both immune and tumor cells. (biomedcentral.com)
  • The CD14+ monocytes exhibited a tolerogenic pattern when co-cultured with hMSCs, with a clear decrease in CD80 and CD86 co-stimulatory molecules, and an increase in the inhibitory receptors ILT-3 and ILT-4. (eurekamag.com)
  • A primary costimulatory signal is delivered through the CD28 receptor after engagement of its ligands, B7-1 (CD80) or B7-2 (CD86). (nih.gov)
  • Recently, molecular homologs of CD28 and CTLA-4 receptors and their B7-like ligands have been identified. (nih.gov)
  • ICOS is a CD28-like costimulatory receptor with a unique B7-like ligand. (nih.gov)
  • On T cells, the cosignaling receptors belong to either the immunoglobulin (CD28-like) or TNF receptor (TNFR) superfamilies. (beckman.com)
  • The CD28 immunoglobulin-superfamily is composed of coinhibitory and costimulatory receptors. (beckman.com)
  • CD28 is expressed by naive and activated T cells and is critical for optimal T cell activation. (rupress.org)
  • In contrast, CTLA-4 is induced upon T cell activation and inhibits T cell activation by binding to B7.1/B7.2, impairing CD28-mediated co-stimulation. (rupress.org)
  • Accordingly, additional CD28 family receptors have been identified. (rupress.org)
  • Principally involved in basic laboratory research, he has studied the B7-CD28 gene family, showing that B7-2/CD28 is the major costimulatory pathway for T cell activation and that PD-L1/PD-1 is the major coinhibitory pathway for T cell activation. (dana-farber.org)
  • CD80 has high affinity for binding to two T cell surface antigens, CD28 and CD152 (CTLA-4). (fishersci.com)
  • The interaction of CD28 and CD152 with CD80 is crucial in T-B cell communication leading to activation of T and B cells, respectively. (fishersci.com)
  • CD80 (B7-1) and CD86 (B7-2) are ligands of T cell critical costimulatory molecule CD28 and of an inhibitory receptor CTLA-4 (CD152). (fishersci.com)
  • Once mobilized, however, T cells begin to express other members of the CD28/B7 receptor family that attenuate the immune response through inhibition of proliferation and cytokine production ( 2 ). (pnas.org)
  • CD28 ligation by B7-1 or B7-2 helps in bringing the T-Cell and Antigen Presenting Cell membranes into close proximity. (wikipathways.org)
  • Besides CD28, many other transmembrane receptors also modulate specific elements of TCR signaling. (wikipathways.org)
  • SIT (SHP2-Interacting Transmembrane Adaptor Protein) and CTLA4 (Cytotoxic T-Lymphocyte Antigen-4) are transmembrane adaptor proteins that interact with the SHP2 (SH2-containing Protein tyrosine Phosphatase-2) and negatively regulate T-cell activation by inhibiting the phosphorylation of Fyn and CD28 respectively. (wikipathways.org)
  • HBV-specific lymphoproliferative, IFN-gamma and IL 10 responses, T cell activation and costimulatory markers (PD1, CTLA4, CD28, CD127), FoxP3+ Treg frequency, and NK frequency and expression of activating/inhibitory receptors and Dendritic cell frequency. (clinicaltrials.gov)
  • Accumulation of CD28 occurs during T-cell activation and has also been shown to induce expression of CTLA4 and increase stability of CTLA4 mRNA. (thermofisher.com)
  • Binding of CTLA4 to PI3K indicates that the co-receptor can generate positive signals in common with CD28. (thermofisher.com)
  • One mechanism involves antagonism of B7-CD28-mediated costimulatory signals by CTLA4, which occurs because CTLA4 has a much higher affinity for B7 than does CD28. (thermofisher.com)
  • Signaling through CD28 promotes cytokine IL-2 mRNA production and entry into the cell cycle, T-cell survival, T-helper cell differentiation and immunoglobulin isotype switching. (thermofisher.com)
  • In addition to the B7/CD28 immune checkpoint regulators, a number of other protein families have also been shown to regulate T cell activation. (rndsystems.com)
  • CD28 interactions with CD80/86 provide the required costimulatory signals. (brainscape.com)
  • deploy a novel T cell engineering strategy, generating a chimeric costimulatory switch receptor (CSR) that circumvents inhibitory signaling in the cancer milieu by fusing the extracellular ligand-binding domain of the co-inhibitory receptor TIGIT to the intracellular stimulatory domain of CD28. (sitcancer.org)
  • In contrast, CD28 tended to be underexpressed in the BAL T cells. (bmj.com)
  • Geng L, Liu J, Huang J, Lin B, Yu S, Shen T, Wang Z, Yang Z, Zhou L, Zheng S. A high frequency of CD8 + CD28 - T-suppressor cells contributes to maintaining stable graft function and reducing immunosuppressant dosage after liver transplantation. (medsci.org)
  • CD8 + CD28 - T cells (CD8Ts) exert immunosuppressive effects in various autoimmune diseases. (medsci.org)
  • CTLA-4 binds to B7 ligands expressed on antigen-presenting cells (APCs) with higher affinity than the costimulatory molecule CD28, and both its gene and surface expression are induced during T cell activation upon APC interaction ( 1 ). (sciencemag.org)
  • ICOS (inducible T-cell costimulatory) belongs to the CD28 family of immune-assisted stimulatory receptors. (prospecbio.com)
  • In co-cultures of peripheral mononuclear blood cells with human MSCs (hereafter referred to as hMSCs), we observed a striking decrease in the level of CD8 expression on CD8+ cells, together with decreased expression of CD28 and CD44, and impaired production of IFN-gamma and Granzyme B. This effect was specific to hMSCs, because it was not observed with several other cell lines. (eurekamag.com)
  • Injection of hMSCs in humanized NSG mice showed similar trends, in particular decreased levels of CD44 and CD28 in human immune cells. (eurekamag.com)
  • The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. (nih.gov)
  • Engagement of CTLA-4 (CD152) by the same B7-1 or B7-2 ligands results in attenuation of T cells responses. (nih.gov)
  • PD-1 is an inhibitory receptor, with two B7-like ligands. (nih.gov)
  • Integration of signals through this family of costimulatory and inhibitory receptors and their ligands is critical for activation of immune responses and tolerance. (nih.gov)
  • Our data demonstrate that the cytoplasmic domain of CTLA-4 has an inherent plasticity for signaling that can be exploited therapeutically with recombinant ligands for this receptor. (jimmunol.org)
  • The interaction of PD-1 with its ligands, PD-L1 and PD-L2, plays a critical role in regulating T cell activation and tolerance. (beckman.com)
  • The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. (rupress.org)
  • The immune system is tightly controlled by co-stimulatory and co-inhibitory ligands and receptors. (rupress.org)
  • The two inhibitory B7 family ligands, PD-L1 and PD-L2, have distinct expression patterns. (rupress.org)
  • Following the discovery of PD-L1 and PD-L2 as the ligands for the PD-1 receptor on T cells, we demonstrated the inhibitory function of PD-L1 and PD-L2 on T cells and showed that blockade of this pathway enhanced T cell activation, proliferation, and cytokine production. (dana-farber.org)
  • Despite CTLA-4 blockade, T-cell proliferation and cytokine production can be inhibited by the interaction of programmed death-1 (PD-1) with its ligands PD-L1 and PD-L2 or by the interaction of PD-L1 with B7-1. (pnas.org)
  • The receptor programmed death-1 (PD-1) is also expressed on T cells following activation, where, on binding to its ligands PD-L1 and PD-L2, it promotes T-cell anergy, apoptosis, and exhaustion. (pnas.org)
  • The programmed cell death pathway includes programmed cell death protein 1 (PD-1) and its ligands programmed death ligands 1 (PD-L1) and 2 (PD-L2). (aspetjournals.org)
  • T cells require binding of their T cell receptor (TCR) to the peptide/human leukocyte antigen complex (pHLA) that is expressed on the target, as well as binding of the T cell costimulatory receptors to their cognate ligands that are expressed by the tumor or antigen presenting cell (APC). (aspetjournals.org)
  • These findings suggest that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3. (bloodjournal.org)
  • For our studies we have developed experimental systems that make it possible to efficiently analyse the contribution of individual ligands to T cell activation processes. (meduniwien.ac.at)
  • In addition we are trying to identify novel receptors and ligands that regulate the activation of T cells by APC. (meduniwien.ac.at)
  • PD-1 is expressed on T-cells, while it's ligands, PD-L1 or PD-L2, are expressed on the surface of tumor cells or antigen presenting cells. (discoverx.com)
  • The absence of known ligands for FCRL4 and Siglec-6 suggests these receptors may regulate BCR signaling through their own constitutive or tonic signaling. (pubmedcentralcanada.ca)
  • These receptors recognize distinct ligands and trigger the activation of specific intracellular signaling pathways, and thus play an important role in the regulation of immune responses ( 7 - 9 ). (pubmedcentralcanada.ca)
  • Although its ligands, if any, are currently unknown, functional analyses of the ITIM-containing intracellular domain of FCRL4 indicated that FCRL4 had a profound negative regulatory effect on B cell receptor (BCR) signaling by inhibiting BCR-mediated calcium mobilization, tyrosine phosphorylation of several intracellular proteins, and activation of MAPK Erk and protein kinase B Akt pathways ( 12 ). (pubmedcentralcanada.ca)
  • Likewise, the virus counteracts NK cell triggering, primarily by suppressing the expression of ligands for activating receptors while preserving engaged inhibitory receptors [7] - [9] . (prolekare.cz)
  • By competing for and binding to B7 ligands, CTLA-4 inhibits T cell proliferation and cytokine expansion. (sciencemag.org)
  • Negative regulatory pathways include expression of inhibitory receptors and corresponding ligands, metabolic dysregulation, recruitment of suppressive cell populations, and T cell-intrinsic anergy. (biomedcentral.com)
  • In Hodgkin lymphoma, alterations of chromosome 9p24 that increase the expression of programed death receptor ligands 1 and 2 (PD-L1 and PD-L2) have been frequently identified and suggest that patients with HL may be uniquely positioned to derive benefit from program cell death receptor 1 (PD-1) blockade with immune checkpoint inhibitors. (onclive.com)
  • The ligands of CCR7 and CCR9 also interact with the atypical receptor CCRL1 (also known as ACKR4), which is expressed in the thymus and has recently been reported to play an important role in normal alpha beta T-cell development. (diva-portal.org)
  • A variant of CD226 that is associated with autoimmune diseases stimulated more VAV1 activity and IL-17 production than did wild-type CD226, demonstrating that VAV1-mediated cross-talk between the CD226 and TCR signaling pathways affects both normal and pathological T cell activation. (sciencemag.org)
  • A series of interconnecting pathways exist within cells which function to repair DNA damage [ 17 ]. (hindawi.com)
  • These same costimulatory pathways can be involved in priming of the immune system as well as execution of tumor cell killing in the tumor microenvironment. (jci.org)
  • As a result, the targeting of these costimulatory pathways has become a primary area of clinical investigation for cancer therapeutics. (jci.org)
  • In particular, checkpoint inhibitor (CPI) antibodies, which block key inhibitory pathways involved in T cell activation, have shown significant clinical potential in a number of solid tumors, leading to extended patient survival ( 2 ). (sciencemag.org)
  • Negative regulatory pathways include extrinsic suppression mechanisms, but also a T cell-intrinsic dysfunctional state. (rupress.org)
  • Data accumulated over the past several years have indicated that tumors with spontaneous antitumor T cell responses have high expression of immune-inhibitory pathways that subvert the effector phase of the response. (rupress.org)
  • Immune checkpoint pathways involve both costimulatory and inhibitory proteins. (biovision.com)
  • Tumor cells can escape the checkpoint pathways to avoid attacks from the immune system. (biovision.com)
  • These results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions, thereby shifting the tumor microenvironment from suppressive to inflammatory. (pnas.org)
  • Although the existence of so many layers of T-cell inhibition may seem surprising, the severe and sometimes fatal autoimmunity that results when even one of these pathways is disrupted attests to their necessity. (pnas.org)
  • Although there are several immune checkpoint pathways that regulate immune cells, to date, the two major approaches to immune checkpoint blockade that have been investigated clinically have targeted cytotoxic-T-lymphocyte antigen (CTLA-4) and the programmed cell death pathway. (aspetjournals.org)
  • Upon initial encounter with its antigen in a lymphoid organ, there are a number of signaling pathways that must be triggered within the T cell to achieve adequate activation. (aspetjournals.org)
  • We use a variety of transgenic and gene knock out mouse models to evaluate the molecular pathways that govern T cell fate. (uhnresearch.ca)
  • Blocking the inhibitory pathways could thus restore the immune system against cancers. (gbiosciences.com)
  • They represent co-signaling pathways which are either costimulatory or coinhibitory. (springermedizin.de)
  • Protein tyrosine phosphorylation subsequently leads to the activation of multiple pathways, including ERK (Extracellular Signal Regulated Kinase), JNK (c-Jun N-terminal Kinase), NF-κB (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFAT(Nuclear Factor of Activated T-Cells) pathways, which ultimately induce effector functions. (wikipathways.org)
  • Activation of T cells via direct stimulation of the T cell receptor or by modulating immune checkpoint pathways are two strategies being employed individually and in combination. (technologynetworks.com)
  • The inhibition may govern through nuclear factor of activated T cells (NFAT), NF‑ kappa B, and AP-1 factors, three major signaling pathways through which TCR regulates gene transcription, which suggesting that B7‑H3 might have more than one receptor on T cells (6). (rndsystems.com)
  • Furthermore, the extent of FCLR4 knockdown effects on BCR-mediated proliferation varied depending on the costimulatory ligand, suggesting that inhibitory receptors may engage specific pathways in inhibiting B cell proliferation. (pubmedcentralcanada.ca)
  • We have found that ectopic expression of Tim-3 in T cells leads to enhancement of T-cell receptor (TCR)-dependent signaling pathways, which was observed at the level of transcriptional reporters and endogenous cytokine production. (asm.org)
  • Here we have demonstrated that two of the more membrane-proximal cytoplasmic tail tyrosines are required for Tim-3 signaling to T-cell activation pathways in a redundant fashion. (asm.org)
  • Tumor cells can exploit these pathways and ultimately elude immunosurveillance by activating these checkpoint receptors via ligand over-expression resulting in T-cell exhaustion. (onclive.com)
  • By combining PD‐L1 silencing with modulators of selected signalling pathways (MAPKs) in dendritic cells, we have increased their anti‐tumour activities, obtaining therapeutic effects with doses 100‐to‐1000‐fold lower than those currently used in experimental cancer models and in human clinical trials. (embopress.org)
  • Engagement of CD226 induced the tyrosine phosphorylation of VAV1 and synergized with T cell receptor (TCR) signals to specifically enhance the production of interleukin-17 (IL-17) by primary human CD4 + T cells. (sciencemag.org)
  • T cell activation is dependent upon signals delivered through the antigen-specific T cell receptor and accessory receptors on the T cell. (nih.gov)
  • and co-stimulatory or co-inhibitory signals. (thefreedictionary.com)
  • In these assays, stable cell lines express luciferase reporters driven by response elements under the precise control of intracellular signals mediated by each co-stimulatory receptor. (aacrjournals.org)
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. (jci.org)
  • b ǀ T cell function may be enhanced through the delivery of exogenous costimulatory signals and blocking co-inhibitory signals. (nih.gov)
  • Agonistic antibodies to 4-1BB and glucocorticoid induced TNFR related protein (GITR) cross-link these activating receptors and bolster T cell effector responses, while blocking antibodies to the co-inhibitory receptors cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed death 1 (PD1) preclude transduction of negative signals and prevent T cell shutdown and anergy. (nih.gov)
  • The costimulatory receptors transduce signals to regulate T-cell activation. (biovision.com)
  • Critical signals for activation are dependent on specific antigens, such as T-cell antigen receptor (TCR) ligation on T cells or on recognition of antibody-coated target cells sensed by FcRγIII (CD16) on natural killer (NK) cells. (aacrjournals.org)
  • Receptor-ligand interactions in the immune synapse are important for maintaining structure (adhesion), conveying bidirectional biochemical signals for activation or inhibition, reorganizing the cytoskeleton, and reorienting the secretory machinery. (aacrjournals.org)
  • signs placed at the side of the arrows indicate activatory and inhibitory signals or unknown functional effects. (aacrjournals.org)
  • The Freeman Laboratory studies the contribution of costimulatory signals to the immune response. (dana-farber.org)
  • Ample evidence now exists that T cells infiltrating tumors can be inhibited by both CTLA-4 and PD-1 coinhibitory signals. (pnas.org)
  • Activation of peroxisome proliferator-activated receptors α and δ synergizes with inflammatory signals to enhance adoptive cell therapy. (uhnresearch.ca)
  • The costimulatory receptors transduce signals to promote immunity against pathogens, whereas the co-inhibitory receptors negatively regulate T-cell activation to prevent self-immunity in normal tissues. (gbiosciences.com)
  • CD5 may serve as a dual receptor, giving either stimulatory or inhibitory signals depending both on the cell type and development stage. (selectscience.net)
  • In thymocytes and B1a cells seems to provide inhibitory signals, in peripheral mature T lymhocytes it acts as a costimulatory signal receptor. (selectscience.net)
  • In the periphery, one important level of regulation is the action of costimulatory signals in concert with TCR (T-Cell antigen Receptor) signals to promote full T-cell activation (Ref. 1). (thermofisher.com)
  • Furthermore, IRIS patients displayed higher serum interferon-γ, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. (bloodjournal.org)
  • NK-cell activity is regulated by an intricate balance of signals transmitted by inhibitory and activating receptors. (bloodjournal.org)
  • Adhesion molecule interactions, two of which (LFA-1/ICAM-1, CD2/LFA-3) are depicted, markedly strengthen the connection between the T cell and APC or target cell so that signals can be sustained. (brainscape.com)
  • These signals can be of co-inhibitory or co-stimulatory nature. (biomedcentral.com)
  • CD81 cross-linking by monoclonal antibody (mAb) specific for CD81 or by immobilized E2 have been shown to result in costimulatory signals for human T cells. (pubmedcentralcanada.ca)
  • These results show that CD81 cross-linking mediates completely different signals in NK cells versus T cells. (pubmedcentralcanada.ca)
  • This is achieved via a highly regulated balance between T-cell co-stimulatory and inhibitory signals, which collectively are known as immune checkpoints. (onclive.com)
  • Through activation of co-stimulatory receptors, or antagonization of inhibitory signals, T-cell responses toward tumor antigens can be enhanced and represent an exciting cancer therapeutic strategy that is transforming the oncology world. (onclive.com)
  • Depending on the signals received, naïve T cells are able to differentiate into mature T cell populations, which play different roles in the immune system. (medicalxpress.com)
  • One example involves the injection of irradiated, cytokine secreting whole tumor cells, after which DCs phagocytose the tumor cells and present tumor antigens in vivo to T cells. (nih.gov)
  • Monoclonal antibodies coat tumor cells and promote phagocytosis through Fc receptors, increasing DC presentation of tumor antigens. (nih.gov)
  • Indeed, T-cell responses elicited to tumor antigens by means of immunogenic tumor cell death are amplified by these immunostimulatory agonist mAbs. (aacrjournals.org)
  • The main mechanism of action is costimulation of CD8+ CTLs cross-primed by dendritic cell against tumor antigens. (aacrjournals.org)
  • Firstly, natural or thymic Tregs (nTregs or tTregs) develop in the thymus through intermediate strength interactions between a self-reacting T cell receptor (TCR) and their cognate antigens, presented by medullary thymic epithelial cells and hematopoietic antigen-presenting cells, leading to upregulation of CD25 [7, 8]. (thefreelibrary.com)
  • The final differentiation or maturation of dendritic cells (DCs) in response to environmental stimuli influences their ability to both initiate immunity and determine the quality of the response to antigens. (pnas.org)
  • Dendritic cells (DCs) are highly differentiated antigen-presenting cells that play a key role in the initiation and regulation of T cell immunity to pathogens and tumors while at the same time preventing immune responses against self-tissues or environmental antigens ( 1 , 2 ). (pnas.org)
  • In addition, targeting of antigens to FcγRs on human DCs, including immune complexes and antibody-coated tumor cells, leads to enhanced generation of both CD4 + and CD8 + T cell responses in culture ( 6 , 14 - 18 ). (pnas.org)
  • Therefore, the targeting of antigens to DCs by means of immune complexes can mediate both maturation of DCs and antigen presentation, leading to immunity that includes cross-presentation of tumors and autoantigens to CD8 + T cells ( 17 , 19 - 23 ). (pnas.org)
  • The T-cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. (thermofisher.com)
  • Furthermore, NK cells from SLE patients do not lyse immature DC efficiently, which may promote the presentation of auto-antigens by DC resulting in the activation of autoreactive T cells. (bmj.com)
  • Here our current focus is the development of systems that allow for studying the regulation of T cell responses to pathogen- and tumour antigens. (meduniwien.ac.at)
  • A, CD4+ T cells (Th1, Th17) recognize antigens of phagocytosed and extracellular microbes and produce cytokines that recruit and activate the phagocytes to kill the microbes. (brainscape.com)
  • B, CD8+ cytotoxic T lymphocytes (CTLs) recognize antigens of microbes residing in the cytoplasm of infected cells and kill the cells. (brainscape.com)
  • CD4+ T cells recognize peptides that are derived from protein antigens and presented by dendritic cells in peripheral lymphoid organs. (brainscape.com)
  • Dendritic cells process antigens and present peptides associated with MHC class II to CD4 T cells and present peptides associated with MHC class I to CD8 T cells. (brainscape.com)
  • 3 They are, however, capable of processing and presenting intact antigens to specific T cell clones (J Grunewald et al , unpublished). (bmj.com)
  • In addition, it has been reported that dendritic cells (DCs) from SLE patients, which are crucial in the modulation of peripheral tolerance to self-antigens, show an increased ratio of activating/inhibitory receptors on their surfaces. (inserm.fr)
  • To examine whether this CD8 + T cell population was likely to represent those recognizing specific antigens, TCR repertoire analysis was performed and indicated TCRβ skewing in the marker positive population, indicating oligoclonality. (biomedcentral.com)
  • Regulatory T cells are one of the types of cells in charge of controlling the immune system in the healthy recognition of self (tolerance) and non-self (foreign) antigens. (medicalxpress.com)
  • This success has captured public imagination and driven academic and industrial researchers to develop similar 'off-the-shelf' receptors targeting shared antigens on epithelial cancers, the leading cause of cancer-related deaths. (investorvillage.com)
  • Receptor-engineered T cells have the potential to cause lethal toxicity from on-target recognition of normal tissues, and there is a paucity of truly tumor-specific antigens shared across tumor types. (investorvillage.com)
  • Gene engineering obviates the requirement for surgery because T cells can be isolated from the blood and receptors conveying specificity for tumor-associated antigens can be introduced using viral and non-viral integration techniques22. (investorvillage.com)
  • Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. (biomedcentral.com)
  • We also observed that both groups of patients presented a significant increase of CD4 + and CD8 + T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. (biomedcentral.com)
  • In addition, cell-cell contact involving programmed death-ligand 1 (PD-L1) resulted in inhibition of T-cell proliferation and induction of T regulatory cells ( 2 , 8 ). (frontiersin.org)
  • Expression of the immune checkpoint Programmed cell Death Ligand-1 (PD-L1) is also increased in TNBC compared to non-TNBC [ 13 ]. (hindawi.com)
  • In this study, we introduce a novel paradigm based on the observation that a bispecific tandem single-chain variable region fragment ligand of CTLA-4 by itself converts this inhibitory receptor into an activating receptor for primary human T lymphocytes. (jimmunol.org)
  • In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. (rupress.org)
  • Schematic receptor-ligand pair interactions of the costimulatory members of the TNF and TNFR families at immune synapses. (aacrjournals.org)
  • We use cellular and molecular immunology techniques, including the cutting-edge gene-editing system CRISPR-Cas9, to elucidate the CD226, TIGIT and CD96 signalling, receptor-receptor and receptor-ligand interactions and study their role in primary human Treg function in health and disease. (ucl.ac.uk)
  • Vaccination with irradiated B16 melanoma cells expressing either GM-CSF (Gvax) or Flt3-ligand (Fvax) combined with antibody blockade of the negative T-cell costimulatory receptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) promotes rejection of preimplanted tumors. (pnas.org)
  • Recently, an additional coinhibitory ligand/receptor interaction has been described that involves binding of PD-L1 on T cells to B7-1 on APCs or vice versa ( 3 ). (pnas.org)
  • In the body, linkage of coinhibitory receptor and ligand suppresses T cell receptor signaling, and limits immune responses. (springermedizin.de)
  • The T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the α and β chains, and a signaling subunit, namely the CD3ε, γ and δ chains and the TCRζ chain. (wikipathways.org)
  • While it is reported that BTLA is a counter receptor for B7S1, further studies are needed to definitely determine the B7-H4 ligand. (thermofisher.com)
  • The ligand of CD161 is the lectin-like transcript 1 (LLT1) [11] , which is detected on activated B cells and TLR-activated pDC and cDCs [12] . (prolekare.cz)
  • Jurkat cells expressing the PD-1 and SHP-1 proteins, each fused to a fragment of our EFC system, are co-incubated with ligand-presenting cells. (discoverx.com)
  • We demonstrate the suitability of the assay for quantifying pathway activation as well as inhibition of PD-1 signaling by both anti-ligand (anti-PD-L1) and anti- receptor (anti-PD-1) antibodies. (discoverx.com)
  • We have identified a murine CMV gene product (m154) that downregulates CD48, a SLAM family member that functions as a ligand of CD244, a molecule involved in the regulation of natural killer (NK) and cytotoxic T cell functions. (prolekare.cz)
  • According to recent clinical studies, tumour growth can be effectively reduced and survival can be improved by blocking the programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD‑L1) pathway. (spandidos-publications.com)
  • In recent studies, the programmed-death receptor-1 (PD-1 and CD279)/programmed-death ligand 1 (PD-L1, B7-H1 and CD274) pathway has been indicated to be critical for regulating T-cell responses and maintaining immune suppression ( 1 - 4 ). (spandidos-publications.com)
  • Here, we show that the interaction between programmed cell death 1 ligand 1 (PD‐L1) on dendritic cells (DCs) and programmed death 1 (PD‐1) on CD8 T cells contributes to ligand‐induced TCR down‐modulation. (embopress.org)
  • We show here that binding of PD‐L1 on dendritic cells to PD‐1 on T cells is implicated in ligand‐induced TCR down‐modulation, by promoting Cbl‐b E3 ubiquitin ligase expression. (embopress.org)
  • found that VAV1 also interacted with the costimulatory molecule CD226. (sciencemag.org)
  • Among these was CD226, a costimulatory molecule of immune cells. (sciencemag.org)
  • It functions as a negative co-stimulatory molecule for the T cell. (thefreedictionary.com)
  • This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). (rupress.org)
  • In parallel, we stained a subset of patients with HCV-specific MHC class I tetramers to compare co-inhibitory molecule expression pattern of HCV-specific CD4+ versus HCV-specific CD8+ T cells. (nature.com)
  • and the immune system inhibitory checkpoint molecule CTLA-4, which inhibits activated T cells from attacking. (ucsf.edu)
  • Within the innate-like T cells, Mucosa-Associated Invariant T (MAIT) cells are restricted by the evolutionarily conserved MHC related molecule, MR1 [5] , [6] . (prolekare.cz)
  • The MR1 molecule presenting these coumpounds is ubiquitously expressed [16] , hence many cell types could have the capacity to activate MAIT cells including non-phagocytic epithelial cells. (prolekare.cz)
  • The title of the webinar is Next Generation Targets for Immuno-Oncology and the key molecule families that will be discussed include the butyrophilins (BTNs), leukocyte immunoglobulin-like receptors (LILRs), and V-set and immunoglobulin domain-containing (VSIGs) proteins. (rndsystems.com)
  • PD-L1 binds to an inhibitory receptor (PD-1), which is a member of the B7 family of receptors ( 4 ), and to the co-stimulatory molecule, CD80 (B7-1) ( 10 ). (spandidos-publications.com)
  • Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
  • However, CD56 dim NK cells can produce cytokines, specifically IFN-γ, after cell triggering via NKp46 of NKp30 activating receptors or after stimulation with combinations of IL-2, IL-12, and IL-15 ( 7 ). (frontiersin.org)
  • c ǀ Immunosuppressive Tregs and myeloid-derived suppressor cells (MDSCs) secrete numerous tolerogenic cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGFβ), inhibiting anti-tumor immune responses. (nih.gov)
  • PD-L1 −/− T cells produce elevated levels of the proinflammatory cytokines in both disease models. (rupress.org)
  • Several stimuli, such as pathogens recognized by means of Toll-like receptors, CD40L, heat shock proteins, inflammatory cytokines, and innate lymphocytes, can lead to DC maturation and T cell immunity ( 2 ). (pnas.org)
  • Engagement of activating FcγRs that contain an immune tyrosine-based activation motif on effector cells, including monocytes, neutrophils, natural killer cells, and mast cells, mediates phagocytosis, antibody-dependent cell-mediated cytotoxicity, and release of cytokines and other inflammatory mediators. (pnas.org)
  • FcεRI is also expressed on antigen-presenting cells , and controls the production of important immune mediators called cytokines that promote inflammation . (wikipedia.org)
  • CD8+ T cells can also secrete some cytokines and participate in similar reactions. (brainscape.com)
  • In the tissues, effector T cells recognize the antigen and respond by secreting cytokines that recruit more leukocytes and activate phagocytes to eradicate the infection. (brainscape.com)
  • Signal 3) that direct T-cell proliferation (IL-2) and differentiation (polarizing cytokines). (brainscape.com)
  • Cytokines can act in an autocrine manner, by stimulating the same cells that produce them, or in a paracrine manner, by stimulating neighbouring cells. (brainscape.com)
  • These cells are key regulators of the immune response secreting pro-inflammatory cytokines and cooperating with B cells for secreting antibodies. (intechopen.com)
  • Inflammatory cytokines, such as IFN gamma, and a combination of phorbol myristate acetate (PMA) and ionomycin induce expression of B7-H3 protein on dendritic cells (DCs) and monocytes (4). (rndsystems.com)
  • Inhibitory receptor downregulation also led to increased levels of HIV-specific antibody-secreting cells and B cell-associated chemokines and cytokines. (pubmedcentralcanada.ca)
  • In addition, CMV alters the function of cytokines and their receptors, and interacts with complement factors. (prolekare.cz)
  • RCC tumor cell lines were treated with different cytokines alone or in combination. (biomedcentral.com)
  • RCC is considered an immunogenic tumor as demonstrated by a high frequency of tumor-infiltrating immune cells, a relatively high incidence of spontaneous recurrences as well as by the efficacy of immunotherapies, like DC-based vaccines, engineered autologous tumor cells, targeting T cell-tumor interaction, stem cell transplantation and treatment with cytokines [ 3 ]. (biomedcentral.com)
  • ICOS stimulates the production of Th1 and Th2 cytokines, however it can also participate in the generation of Th2 cells. (prospecbio.com)
  • Confocal microscopy experiments showed increased binding of NK receptor-coated beads to infected cells expressing the appropriate class I MHC proteins. (jimmunol.org)
  • In addition, specific cell-free bead aggregates covered with class I MHC proteins were observed only in infected cells. (jimmunol.org)
  • The main lysis receptors include the NKp46, NKp44, and NKp30 proteins ( 3 ). (jimmunol.org)
  • Three different types of inhibitory receptors inhibit NK cytotoxicity via interaction with class I MHC proteins ( 6 ), including the killer cell Ig-like receptor (KIR) family ( 6 , 7 ), the C-type lectin family ( 7 ), and the Ig-like transcript/leukocyte Ig-like receptor (LIR) family ( 8 ). (jimmunol.org)
  • NK cell cytotoxicity can be also inhibited in a class I MHC-independent manner, e.g., via the homotypic interactions of CEACAM1 proteins ( 9 , 10 ). (jimmunol.org)
  • The KIR2DL1 recognizes HLA-C proteins containing lysine at position 80 ( 11 , 12 ), and the LIR1 receptor recognizes a broad spectrum of class I MHC proteins. (jimmunol.org)
  • As their retrovirus cousins, lentivectors are devoid of viral proteins, stably incorporate their genome into the host cell, and lead to long-term transgene expression. (hindawi.com)
  • In this study, we show that the Egr2-driven cell surface proteins LAG-3 and 4-1BB can identify dysfunctional tumor antigen-specific CD8 + TIL. (rupress.org)
  • These receptors lack any intrinsic enzymatic activity and their signal transduction relies on associations with TNFR-associated factor (TRAF) adaptor proteins. (aacrjournals.org)
  • After incubation with cell lysates, only phospho-ALK or phospho-NPM-ALK proteins are captured by the coated antibody. (cellsignal.com)
  • All the above components along with accessory proteins essential for MHC are a part of the immunological synapse that initiates T-cell activation. (wikipathways.org)
  • CD45 plays a role in antagonizing the effect of inhibitory proteins on T-cell activation. (wikipathways.org)
  • BACKGROUND Mammalian Toll-like receptor (TLR) proteins are pattern recognition receptors for a diverse array of bacterial and viral products. (bmj.com)
  • Mammalian Toll-like receptor (TLR) proteins are a new family of proteins that share sequence similarity with the Drosophila Toll receptor proteins. (bmj.com)
  • TLR4 appears to be unique among the TLR proteins in that it uses two additional proteins, CD14 and MD-2, as co-receptors. (bmj.com)
  • 4-6 The intracellular domain of all TLR proteins is highly conserved, and shares substantial sequence similarity with both the interleukin (IL) 1 and IL18 receptors. (bmj.com)
  • 7 This conserved intracellular domain has been termed the Toll interleukin receptor domain and it mediates the signal transducing capacities of the TLR and IL1 receptor proteins. (bmj.com)
  • The costimulatory CTLA4 pathway, attenuates or downregulates T-cell activation, and CTLA4 is designed to remove body cells displaying a foreign epitope, such as virus-infected cells, cells containing intracellular bacteria, and cancer cells with mutant surface proteins. (thermofisher.com)
  • Another mechanism for the inhibitory activity of CTLA-4 involves direct interactions with TCR-CD3 complex at the immunological synapse and also the proteins involved in downstream signaling after TCR activation. (thermofisher.com)
  • These include members of the butyrophilin , CD2/SLAM , TIM , CD226 , and LILR families, along with TNF receptor superfamily proteins. (rndsystems.com)
  • However, developing drugs targeting these checkpoint proteins has proved to be quite challenging, as cell-based assays used to screen for functional drugs are often difficult to create, involve the use of human primary cells, and have long, complicated protocols. (discoverx.com)
  • Both murine and human B7-H3 fusion proteins fail to bind to resting T cells, but can recognize activated T cells which stimulated with PHA or ConA, indicating that B7-H3 receptors are induced upon T cell activation (5). (rndsystems.com)
  • Gene expression profiling and Egr2 ChIP-Seq analysis revealed multiple Egr2-driven cell surface proteins in T cell anergy, including the inhibitory receptor Lag3, but also the costimulatory receptor 4-1BB. (biomedcentral.com)
  • We examined whether these surface proteins might be useful for identifying the dysfunctional tumor-reactive CD8 + T cells within the tumor microenvironment. (biomedcentral.com)
  • Immune suppressive checkpoint proteins have been identified that negatively regulate the immune system, resulting in suppressed T-cell inflammatory responses and prevention of autoimmunity (CTLA-4, PD-1, LAG-3, TIM-3, KIRs). (onclive.com)
  • Here we discuss how tumor cell intrinsic immune responses to loss of DNA repair result in modification of the tumor microenvironment and are associated with lymphocytic infiltration. (hindawi.com)
  • A lack of the chemokine CCL4 within the tumor microenvironment leads to the absence of CD103 + dendritic cells (DCs), a crucial cell population influencing CPI responsiveness. (sciencemag.org)
  • Much of the work done dissecting CD8 + T cell dysfunction in the tumor microenvironment has been translated from chronic infection examples, such as the chronic LCMV mouse model ( Pauken and Wherry, 2015 ). (rupress.org)
  • Myeloid-derived suppressor cells (MDSCs) populating the tumor microenvironment can express both B7-1 and PD-L1 ( 4 ). (pnas.org)
  • In addition we are focused on how the tissue or tumor microenvironment can have a significant impact on T cell responses. (uhnresearch.ca)
  • Expression of costimulatory and inhibitory receptors in FoxP3+ regulatory T cells within the tumor microenvironment: Implications for combination immunotherapy approaches. (uhnresearch.ca)
  • The antitumor effects of CD8 + T cells can be blocked in the tumor microenvironment, including through the suppressive function of regulatory T cells (T regs ). (sciencemag.org)
  • High serum IL-8 levels have been shown to correlate with poor prognosis in several cancers, and the cytokine is known to contribute to disease progression by inducing angiogenesis, recruiting neutrophils and myeloid-derived suppressor cells to the tumor microenvironment, enhancing tumor "stem-ness," and promoting the epithelial-mesenchymal transition. (sitcancer.org)
  • Thus, IL-4 and TNFα, which could be released by immune cells of the tumor microenvironment, are able to control the B7-H1 expression in RCC thereby altering T cell responses. (biomedcentral.com)
  • The emergence of immune checkpoint inhibitors as an effective treatment strategy is a result of increased understanding of the elaborate relationship between tumor cells, their microenvironment and the host immune response. (onclive.com)
  • Hodgkin lymphoma is characterized by a small number of characteristic neoplastic Reed- Sternberg cells coupled with a dense ineffective inflammatory tumor microenvironment. (onclive.com)
  • Using a novel methodology of epigenetic quantitative analysis, Dartmouth-Hitchcock's Norris Cotton Cancer Center's interdisciplinary team of investigators led by Camilo Fadul, MD, found no correlation between regulatory T cells (Tregs) and survival in the tumor microenvironment or blood, even when adjusting for well-known prognostic factors. (medicalxpress.com)
  • Engagement of CD226 activated VAV1, which in turn enhanced the TCR-dependent production of the proinflammatory cytokine IL-17 by human T cells. (sciencemag.org)
  • Both strategies result in boosted T cell effector function, including cytokine release and cytotoxicity. (nih.gov)
  • Strategies to inhibit immunosuppressive cytokine secretion or kill Tregs and MDSCs diminish immune suppression and promote T cell mediated tumor destruction. (nih.gov)
  • A soluble VISTA-Ig fusion protein or VISTA expression on APCs inhibits T cell proliferation and cytokine production in vitro. (rupress.org)
  • The co-stimulatory receptor OX40 is upregulated on T cells following activation and increases their clonal expansion, survival and cytokine production when engaged. (nih.gov)
  • The NK receptor, CD161, highly expressed by MAIT cells, modulated the cytokine but not the cytotoxic response triggered by bacteria infected cells. (prolekare.cz)
  • Accordingly, they express at their cell surface high levels of cytokine receptors for IL-18, IL-12 and IL-23 [8] , [9] . (prolekare.cz)
  • To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of antiretroviral therapy. (bloodjournal.org)
  • Moreover, PD-1 + CD4 + T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. (bloodjournal.org)
  • The antitumor activity of the CD8 + T cells was inhibited by the presence of tumor-derived T regs , which depended on cell-cell contact or close proximity, required the cytokine TGF-β on the T reg cell surface, and resulted in the increased cell surface expression of the immune checkpoint receptor PD-1 on the CD8 + T cells. (sciencemag.org)
  • Whereas Tim-3 has been used to identify dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully responsive with respect to cytokine production and cytotoxicity. (bloodjournal.org)
  • 3 CD56 bright CD16 − NK cells produce abundant IFN-γ in response to stimulation with interleukin (IL)-12 and proliferate robustly when cultured in IL-2, whereas CD56 dim CD16 + NK cells are more cytolytic and produce significant amounts of cytokine when their activating receptors are engaged. (bloodjournal.org)
  • T cells co-transduced with both an antigen receptor and the CSR displayed enhanced cytokine production in vitro and prolonged survival in xenograft models of established melanoma. (sitcancer.org)
  • α/βR −/− λR −/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. (asm.org)
  • This might be partially explained by the yet incomplete picture of cellular alterations in tumor cells upon cytokine treatment investigated in detail in this study. (biomedcentral.com)
  • A mcherry reporter gene construct containing B7-H1 promoter was cloned and its activity was determined upon transfection in cytokine-stimulated cells. (biomedcentral.com)
  • Cytokine pretreated tumor cells were co-cultured with allogeneic CD8 + T cells from healthy donors and T cell proliferation as well as cytokine secretion was determined. (biomedcentral.com)
  • Despite HLA class I and LFA-1 were also increased, the cytokine-mediated up-regulation of B7-H1 was more pronounced and caused an inhibition of allospecifc CD8 + T cell proliferation. (biomedcentral.com)
  • The interaction of B7-H2 / ICOS takes a vital role in T-cell differentiation, T-B cell interaction in addition to humoral immune response is essential for the formation of reproductive centers as well as the production of cytokine IL-4. (prospecbio.com)
  • Moreover, ICOS is more effective in inducing IL-10 production, a cytokine which is important for the inhibitory function of T regulatory cells. (prospecbio.com)
  • Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells. (biomedcentral.com)
  • SIGLECs are members of the immunoglobulin superfamily that are expressed on the cell surface. (wikipedia.org)
  • All of the Fcγ receptors (FcγR) belong to the immunoglobulin superfamily and are the most important Fc receptors for inducing phagocytosis of opsonized (marked) microbes. (wikipedia.org)
  • [10] It is composed of two extracellular Ig-like domains, and is a member of both the immunoglobulin superfamily and the multi-chain immune recognition receptor (MIRR) family. (wikipedia.org)
  • With one Ig-like domain in its extracellular portion, this Fc receptor is also a member of the immunoglobulin superfamily. (wikipedia.org)
  • the high-affinity receptor FcεRI is a member of the immunoglobulin superfamily (it has two Ig-like domains). (wikipedia.org)
  • The T-cell immunoglobulin- and mucin domain-containing (Tim)-3 receptor was initially identified as a T-helper 1-specific type I membrane protein involved in regulating T-cell responses. (bloodjournal.org)
  • This is further supported by recent data demonstrating the dynamics of expression of the killer immunoglobulin-like receptors (KIR), CD57, CD94, and CD62L expression on the CD56 dim CD16 + NK cells as they mature from CD56 bright CD16 - NK-cell precursors. (bloodjournal.org)
  • T-cell immunoglobulin- and mucin domain-containing (Tim)-3 is a member of Tim family of receptors of which there are 3 in humans (Tim-1, Tim-3, and Tim-4). (bloodjournal.org)
  • The antibody BU63 reacts with CD86 (B7-2), a 70 kDa type I transmembrane glycoprotein of immunoglobulin supergene family, expressed on professional antigen-presenting cells, such as dendritic cells, macrophages or activated B lymphocytes. (antibodies-online.com)
  • Like many other immunoglobulin receptors, PD-1 harbors immunoreceptor tyrosine inhibitory motifs (ITIMs) in it's cytoplasmic tail that are important signaling motifs. (discoverx.com)
  • They mediate cell-cell and cell-matrix adhesion and can be grouped into distinct families based on their structures-for example, the integrins and members of the immunoglobulin superfamily. (bmj.com)
  • To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. (sciencemag.org)
  • NK cells are now accepted to play an important role in both the adaptive and innate immune responses that govern infection, autoimmunity, and tumor immunosurveillance ( 2 , 3 ). (frontiersin.org)
  • However, newer treatments have shifted attention to targets on immune cells, resulting in dramatic responses. (hindawi.com)
  • Efficient DNA damage responses such as cell cycle arrest and repair are therefore essential in order to maintain genomic integrity and stability [ 2 ]. (hindawi.com)
  • However, responses to immunotherapy are not restricted to TNBC, with responses observed in the neoadjuvant setting in both TNBC and hormone-receptor positive breast cancer [ 15 ], and in PD-L1 positive trastuzumab-resistant HER2 positive breast cancer [ 16 ]. (hindawi.com)
  • CTLA-4 is an activation-induced, transmembrane glycoprotein in T lymphocytes that inhibits the responses of these cells when coligated with their clonotypic Ag receptors (TCR) ( 1 , 2 ). (jimmunol.org)
  • As such, CTLA-4 has emerged as a very attractive target for immunomodulatory drugs that block its inhibitory function and enhance T cell-mediated immunity ( 6 ), or alternatively, enhance its inhibitory function and suppress unwanted immune responses ( 4 , 7 ). (jimmunol.org)
  • The human immune system is regulated by a broad network of co-inhibitory and co-stimulatory receptors that control the type, scale, and duration of immune responses. (aacrjournals.org)
  • Fully human monoclonal antibodies targeting CTLA-4 have been shown to increase T cell function and antitumor responses in patients with advanced metastatic melanoma. (jci.org)
  • Recently retroviral and lentiviral vectors have been used to generate tolerogenic dendritic cells, key professional antigen presenting cells that regulate immune responses. (hindawi.com)
  • A VISTA-specific monoclonal antibody interferes with VISTA-induced suppression of T cell responses by VISTA-expressing APCs in vitro. (rupress.org)
  • In contrast, PD-1 (programmed death 1) negatively regulates T cell responses. (rupress.org)
  • Post-surgical pain scores and inflammatory responses measured by white blood cell, neutrophil, and lymphocyte counts were assessed. (medsci.org)
  • CD4+ Regulatory T cells (Tregs) are crucial to maintain tolerance, balancing effector T cell responses to harmful agents and suppressing unwanted responses. (ucl.ac.uk)
  • Dr. Allison's research focuses on the mechanisms that govern T cell responses and applying that basic understanding to overcome cancer's evasion of attack by the immune system. (ucsf.edu)
  • Overall, NLF CD56dim cells are a unique cell population that likely play a role in orchestrating innate immune responses in the nasal cavity, which is distinct from their role as a non-antigen-restricted cytotoxic CD56dim lymphocytes in the PB. (deepdyve.com)
  • The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses and prevent autoimmunity, however, tumors exploit this pathway to escape from immune destruction. (nih.gov)
  • The physiologic consequences of cell-bound IgG and immune complexes are modulated by a balance between activating and inhibitory Fcγ receptors (FcγRs) and include immune regulatory and inflammatory responses ( 7 - 10 ). (pnas.org)
  • In particular, we examine how to promote T cell responses to tissues, with a goal to understand and control autoimmune and anti-tumor immune responses. (uhnresearch.ca)
  • ILC regulation of T cell responses in inflammatory diseases and cancer. (uhnresearch.ca)
  • Our interest in NK cells stems from their ability to directly lyse infected and tumor cells and to mediate antibody-dependent cellular cytotoxicity, acting as a bridge between innate and adaptive immune responses. (stanford.edu)
  • These investigations focus broadly on T cell, antibody, and NK cell responses to viruses during pregnancy, and use infection and vaccination as models. (stanford.edu)
  • These findings suggest that inhibitory receptors can modulate the efficacy of immune responses against gammaherpesvirus infections. (uni-muenchen.de)
  • B7-H4 is expressed primarily on the membrane of lymphoid cells, and as an immunoinhibitory protein that interacts with receptors on the surface of T lymphocytes, it is involved in mediating cellular and humoral immune responses. (thermofisher.com)
  • This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects. (jove.com)
  • More than 80% of subjects with either DRB1*0401 or DRB1*0301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope. (jove.com)
  • [13] [14] As a result of its cellular distribution, this receptor plays a major role in controlling allergic responses . (wikipedia.org)
  • 11 Tim-3 is a type I transmembrane protein that contains no defined signaling motifs in its cytoplasmic domain, but it has been implicated both in activation and inhibition of immune responses 12 , 13 and in the induction of apoptosis of Tim-3-bearing cells through interactions with galectin-9. (bloodjournal.org)
  • Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, often exploited by many cancers. (discoverx.com)
  • Therefore, therapeutics that block inhibitory receptors have proved to be powerful agents to restore anti-tumor immune responses. (discoverx.com)
  • The second article addresses the ongoing question of how T cell responses determine outcomes of checkpoint inhibition. (sitcancer.org)
  • Dendritic cells are efficient with regard to antigen presenting capacity and are probably critical in primary immune responses, while alveolar macrophages have generally been considered to have poor antigen presenting capacity 2 and may even suppress T cell proliferation. (bmj.com)
  • Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. (pubmedcentralcanada.ca)
  • These findings on HIV-associated B cell exhaustion define potential targets for reversing the deleterious effect of inhibitory receptors on immune responses against persistent viral infections. (pubmedcentralcanada.ca)
  • These features include increased expression of multiple inhibitory receptors, as well as poor proliferative and effector responses to a variety of stimuli. (pubmedcentralcanada.ca)
  • The generation of an efficient host-elicited immune response against CMV includes the induction of natural killer (NK) cells, antibody and T-cell mediated responses [3] . (prolekare.cz)
  • B7 family members are mainly described to modulate T cell responses as second signal in cooperation with the first signal, the antigen recognition mediated by binding of the T cell receptor (TCR) with the major histocompatibility complex (MHC). (biomedcentral.com)
  • The transmembrane protein Tim-3 has been shown to negatively regulate T-cell-dependent immune responses and was recently demonstrated to be associated with the phenomenon of immune exhaustion, which can occur as a consequence of chronic viral infection. (asm.org)
  • Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blockade can promote antitumor T cell immunity and clinical responses. (sciencemag.org)
  • Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a co-inhibitory receptor that controls T cell activation during initiation and maintenance of adaptive immune responses. (sciencemag.org)
  • ICOS forms homodimers and takes a significant part in immune responses, cell-cell signaling, as well as regulation of cell proliferation. (prospecbio.com)
  • The local and distant immune responses elicited by radiation therapy can have disparate effects on tumor activity: resulting either in continued tumor growth or tumor cell death. (onclive.com)
  • regulatory T cells combat this effect by suppressing excessive immune responses and responses against our own bodies. (medicalxpress.com)
  • Regulatory T cells (Tregs) function to suppress immune responses of other cells, and their dysfunction has been associated with development of immune disorders. (medicalxpress.com)
  • Verastem announced that a poster highlighting the synergistic effects of duvelisib in combination with immune checkpoint or co-stimulatory antibodies in preclinical models of B cell lymphoma was presented at ASCO-SITC Clinical Immuno-Oncology Symposium being held January 25-27. (thefreedictionary.com)
  • Here, we show that selective blockade of the inhibitory Fcγ receptor (FcγR) FcγRIIb with recently developed monoclonal antibodies leads to maturation of human monocyte-derived DCs, which depends on the presence of IgG in normal human plasma. (pnas.org)
  • Therefore, the activation status of DCs in the presence of normal human serum depends on the balance between activating and inhibitory FcγRs and can be enhanced by new antibodies that react selectively with FcγRIIb. (pnas.org)
  • Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies. (aspetjournals.org)
  • CD5 is the phenotypic marker of a B cell subpopulation involved in the production of autoreactive antibodies.Disease relevance: CD5 is a phenotypic marker for some B cell lymphoproliferative disorders (B-CLL, Hairy cell leukemia, etc. (selectscience.net)
  • Treatment with neutralizing antibodies that target inhibitory receptors, or "checkpoint blockade," has proven effective in reversing disease severity in a variety of mouse models for chronic viral infection and cancer ( 20 , 21 ). (asm.org)
  • Fc receptors bind to antibodies that are attached to infected cells or invading pathogens . (wikipedia.org)
  • Monoclonal antibodies directed against the T cell co-inhibitory receptors, CTLA-4 and PD-1 have been shown to have potent anti-tumor effects, suggesting that other immune checkpoint regulators may also serve as immunotherapeutic targets. (rndsystems.com)
  • However, when Tim-3 was cross-linked with antibodies it suppressed NK cell-mediated cytotoxicity. (bloodjournal.org)
  • These data are of importance for understanding the complex interplay of tumor cells with immune cells orchestrated by a number of different soluble and membrane bound mediators and for the implementation of check point antibodies directed against B7-H1. (biomedcentral.com)
  • Therefore, monoclonal antibodies (mAb) targeting PDL1/B7-H1 on tumor cells or the PD1 receptor expressed by immune cells have been developed for the treatment of tumors. (biomedcentral.com)
  • Monoclonal antibodies (mAbs) that block CTLA-4 interactions with B7 may enhance effector T cell (T eff ) function ( 2 ) and may also inhibit regulatory T cell (T reg ) activity ( 3 , 4 ), leading to regression of established tumors in mouse models ( 5 ). (sciencemag.org)
  • Because CTLA-4 is constitutively expressed on T regs , antibodies that bind CTLA-4 have also been recently reported to operate independently of CTLA-4-B7 interactions by triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and Fc receptor-mediated elimination of T regs within tumors in mouse models ( 6 - 8 ). (sciencemag.org)
  • Irrefutable evidence that an entirely immunologic approach can cause regression of a wide array of human cancers has come from the recent success of using monoclonal antibodies (mAbs) targeting checkpoints of immune activation, including cytotoxic T lymphocyte-associated protein 4 (CTLA-4) (ref. 1) and programmed cell death protein 1 (PD-1) (ref. 2). (investorvillage.com)
  • Conditioning of antigen-specific T-cells by activated and antigen-pulsed MSCs prevented T-cells to proliferate upon subsequent activation by dendritic cells, even after removal of the MSCs. (frontiersin.org)
  • The splenic CD8(+) T cells from combined mAb treated mice produced high levels of IFN-γ upon tumor antigen stimulation and exhibited antigen-specific cytolytic activity. (nih.gov)
  • On one hand, it regulates the activation of the adaptive immune system and the breach of self-tolerance, as antigen presenting cells (APCs), especially dendritic cells, are essential for the activation of naïve antigen specific T cells, a crucial step in the development of autoimmunity. (medworm.com)
  • Prior studies by Kalergis and Ravetch ( 25 ) have shown that targeting immune complexes to DCs from mice genetically lacking inhibitory FcγRIIb can lead to enhanced generation of antigen-specific CD8 + T cell immunity in vitro and in vivo . (pnas.org)
  • Gupta, Sorab 2018-05-04 00:00:00 Chimeric antigen receptor (CAR) T cell therapy is genetically engineered tumor antigen-specific anticancer immunotherapy, which after showing great success in hematological malignancies is currently being tried in advanced solid tumors like pancreatic cancer. (deepdyve.com)
  • CD5 modulates signaling through the antigen-specific receptor complex (TCR and BCR). (selectscience.net)
  • Regulatory T cells (T regs ) suppress antitumor immunity by inhibiting the killing of tumor cells by antigen-specific CD8 + T cells. (sciencemag.org)
  • During the expansion phase of an immune response to acute infection, newly activated antigen-specific T cells expand rapidly and acquire effector functions. (asm.org)
  • antigen‐specific inflammatory arthritis and a T cell‐derived lymphoma. (embopress.org)
  • However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
  • Activated HLA-DR3-expressing MSCs pulsed with GAD65 peptide inhibited proliferation of HLA-DR3-restricted GAD65-specific T-cells, while this HLA class II expression did not induce cellular alloreactivity. (frontiersin.org)
  • These mechanisms include recruitment of suppressor immune cells, such as Tregs, myeloid-derived suppressor cells that impair T cell proliferation, and tumor-associated macrophages, which appear to have both tumoricidal and tumorostatic functions. (jci.org)
  • Engagement of these receptors is typically associated with proliferation, elevated effector functions, resistance to apoptosis, and differentiation into memory cells. (aacrjournals.org)
  • The fraction of tumor-infiltrating Teffs expressing CTLA-4 and PD-1 increases, reflecting the proliferation and accumulation of cells that would otherwise be anergized. (pnas.org)
  • In addition, FBXL10 is over-expressed in various cancers where it functions to induce cell proliferation and repress senescence through repression of the p15Ink4b gene locus (6-8). (cellsignal.com)
  • High expression of FBXL10 in pancreatic ductal adenocarcinoma is associated with metastasis, while high expression in acute myeloid leukemia is associated with increased proliferation and self-renewal of leukemic stem cells (6-8). (cellsignal.com)
  • Although B7-H4 binds an unknown receptor, it is thought to deliver an inhibitory signal to T-cells preventing their proliferation, cell cycle progression and interleukin-2 production. (thermofisher.com)
  • Moreover, it has been found that NK cells are able to inhibit T cell proliferation by lysing dendritic cells (DC). (bmj.com)
  • As the infection progresses, the adaptive immune system respond to compounds produced by these pathogens in a process that requires priming of naïve cells and subsequent proliferation and differentiation. (prolekare.cz)
  • B7-H3 was reported to act as a co-stimulatory regulator to enhance the proliferation of both CD4 + and CD8 + T cells, the induction of cytotoxic T cells, and IFN-gamma production in the presence of TCR signaling (1). (rndsystems.com)
  • Here, we show that downregulation of B cell inhibitory receptors in primary human B cells led to increased tissue-like memory B cell proliferation and responsiveness against HIV. (pubmedcentralcanada.ca)
  • In human B cells, siRNA knockdown of 9 known and putative B cell inhibitory receptors led to enhanced B cell receptor-mediated (BCR-mediated) proliferation of tissue-like memory but not other B cell subpopulations. (pubmedcentralcanada.ca)
  • Indeed, an in vitro suppression assay revealed that these cells are capable of inhibiting proliferation of conventional T cells with a potency similar to that seen with FoxP3 + regulatory T cells. (biomedcentral.com)
  • CD8+ cells that were preconditioned by MSCs had similar effects on monocytes and were able to inhibit lymphocyte proliferation. (eurekamag.com)
  • Novel APC-like properties of human NK cells directly regulate T cell activation. (bmj.com)
  • Most of the additional B7 family members have also been shown to regulate T cell activation but many of their receptors have yet to be identified. (rndsystems.com)
  • However, a comprehensive understanding of the regulatory circuits governing their function and the cell type-specific mechanisms by which they contribute to the development of metabolic syndrome is lacking. (europa.eu)
  • Specifically, we aim to (a) decipher the global regulatory landscape and interaction networks of WAT hematopoietic cells at the single-cell level, (b) identify new mediators of WAT immune cell contributions to metabolic homeostasis, and (c) decode how host-microbiome communication shapes the development of WAT inflammation and obesity. (europa.eu)
  • Functional analysis revealed defective IL-2 and TNF production yet retained expression of IFN-γ and regulatory T cell-recruiting chemokines. (rupress.org)
  • The mechanisms of action depend on a complex interplay of CTL, T-helper cells, regulatory T cells, dendritic cells, and vascular endothelium in tumors. (aacrjournals.org)
  • Dr. Anne M Pesenacker's research focuses on how regulatory T cell (Treg) function is controlled in health versus autoimmunity. (ucl.ac.uk)
  • The immune homeostasis associated with periodontal health requires a regulated immuno-inflammatory response, during which the presence of immune regulatory cells is essential to ensure a response that minimizes collateral tissue damage [3]. (thefreelibrary.com)
  • Although different T cell types with regulatory functions have been identified, the most physiologically relevant Treg population is characterized as [CD4.sup. (thefreelibrary.com)
  • Combination PD-1 and CTLA-4 blockade increases effector T-cell (Teff) infiltration, resulting in highly advantageous Teff-to-regulatory T-cell ratios with the tumor. (pnas.org)
  • Malignant transformation was classically defined by the ability to avoid the normal regulatory mechanisms of cell growth, division, and death. (pnas.org)
  • Turning the Tide Against Regulatory T Cells. (uhnresearch.ca)
  • Within the T cell compartment, the proportion of effector memory and late effector subsets of CD4 and CD8 T cells was increased, together with transient increases in proportions of CD45RA-regulatory T cells (Tregs ) and T helper type 1 (Th1 cells) and a decrease in Th17·1 cells. (stanford.edu)
  • However, NK cells regulatory function in SLE has not been evaluated. (bmj.com)
  • Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. (bloodjournal.org)
  • In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. (bloodjournal.org)
  • 7 The possibility of a lack of appropriate regulatory T-cell (Treg) response because of inadequate numbers of Treg has also been investigated. (bloodjournal.org)
  • A comparison with recipients who showed failure of immunosuppressant withdrawal suggested that an increased proportion of regulatory T (Treg) cells is a crucial distinguishing immune characteristic( 8 ). (medsci.org)
  • transferred enriched, ex vivo-expanded regulatory T-cell into 10 consecutive adult recipients early post-LT. At the end of the pilot study, these candidates were immunosuppressant free for more than 1 year, revealing that regulatory T-cell-based cell therapy was safe and effective for drug minimization and induction of operational tolerance in LT( 9 ). (medsci.org)
  • Titled, "Regulatory T Cells Are Not a Strong Predictor of Survival for Patients with Glioblastoma," the findings were published in Neuro-Oncology . (medicalxpress.com)
  • The Dartmouth investigators hypothesize that an immune "net score," which takes into account the proportion of regulatory and effector immune cells as well as the expression of co-stimulatory and inhibitory receptors by both cancer and immune cells, will be a useful indicator of the patient's immune status with prognostic and therapeutic implications. (medicalxpress.com)
  • Here we offer our perspective on how expanding the use of genetically redirected T cells to treat the majority of patients with solid cancers will require major technical, manufacturing and regulatory innovations centered around the development of autologous gene therapies targeting private somatic mutations. (investorvillage.com)
  • Indeed, recent experience with sipuleucel-T, a gene-modified cell product for prostate cancer, demonstrated the feasibility of having a patient's immune cells collected, sent to a central manufacturing facility, and returned back for re-infusion in a manner that gained US Food and Drug Administration (FDA) regulatory approval23. (investorvillage.com)
  • Collectively, a framework of manufacturing feasibility, regulatory precedent and vector safety is now in place and it is possible to envi-sion treating large numbers of cancer patients using gene-engineered T cells. (investorvillage.com)
  • Costimulation ( 1 ) is therefore a pathway of intercellular communication that depends on the expression of complementary glycoproteins on the surface of interacting cells. (aacrjournals.org)
  • First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
  • This results in a population of migrating effector CD8 + T-lymphocytes and the second small population called central memory T-cells that remains in the secondary lymphatic organs and the bone marrow. (wikipedia.org)
  • T lymphocytes that constitutively express the IL-2 receptor a-chain, CD25, and the transcription factor Foxp3, comprising approximately 10% of the [CD4.sup. (thefreelibrary.com)
  • Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. (uhnresearch.ca)
  • In vitro-generated MART-1-specific CD8 T cells display a broader T cell receptor repertoire than naïve ex vivo and tumor infiltrating lymphocytes. (uhnresearch.ca)
  • CD5 is expressed on all mature T-lymphocytes, most of thymocytes, subset of B-lymphocytes and on many T-cell leukemias and lymphomas. (selectscience.net)
  • The CTLs (Cytotoxic T-Lymphocytes) are able to kill these cells by inducing a programmed cell death known as apoptosis (Ref. 3 & 4). (thermofisher.com)
  • Background Natural killer (NK) cells are large granular lymphocytes that belong to the innate immunity. (bmj.com)
  • Mucosal associated invariant T cells (MAIT) are innate T lymphocytes that detect a large variety of bacteria and yeasts. (prolekare.cz)
  • Natural killer (NK) cells are innate lymphocytes that play an important role against viral infections and cancer. (bloodjournal.org)
  • Human NK cells transcribe the highest amounts of Tim-3 among lymphocytes. (bloodjournal.org)
  • The T lymphocytes are stimulated to proliferate and differentiate into effector (and memory) cells, which enter the circulation and migrate to sites of infection in peripheral tissues. (brainscape.com)
  • There were also increased numbers of BAL lymphocytes whose phenotypic characteristics have earlier been associated with clonally expanded, replicatively senescent cells of the Th1 type. (bmj.com)
  • when PD-1 ligates with tumour-associated PD-L1, the apoptosis or downregulation of effector cytotoxic T lymphocytes is induced, thereby resulting in an escape from T-cell-mediated immune surveillance ( 11 ). (spandidos-publications.com)
  • The mechanisms underlying the immunomodulatory effects of mesenchymal stem cells (MSCs) have been investigated under extreme conditions of strong T cell activation, which induces the rapid death of activated lymphocytes. (eurekamag.com)
  • Historically, pro-curing antitumor T cells for use in ACT has come from the surgical removal of a cancer metastasis in order to obtain tumor-infiltrating lymphocytes (TILs). (investorvillage.com)
  • Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors. (frontiersin.org)
  • APX005M is a novel, humanised investigational monoclonal antibody designed to overcome the systemic immune suppression that typically affects cancer patients through activation of CD40, a co-stimulatory receptor on the antigen presenting cells that is essential for activating both innate and adaptive immunity. (thefreedictionary.com)
  • Fully owned owned by Alligator, ATOR-1015 binds to two different immune receptors: the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. (thefreedictionary.com)
  • B cells require a co-stimulatory signal together with antigen recognition for B cell activation. (thefreedictionary.com)
  • To address this, we have developed a suite of cell line-based reporter bioassays for co-stimulatory immune checkpoint targets including GITR, 4-1BB, OX40, and CD40. (aacrjournals.org)
  • These bioassays reflect mechanisms of action for drug candidates designed for each co-stimulatory receptor and demonstrate high specificity, sensitivity and reproducibility. (aacrjournals.org)
  • Transcriptional and phenotypic characterization revealed coexpression of multiple additional co-stimulatory and co-inhibitory receptors. (rupress.org)
  • Conversely, expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific CD4+ T cells during chronic infection. (nature.com)
  • Here, we present a comprehensive analysis of the expression pattern of TIGIT of HCV-specific CD4+ T cells as part of a network of co-inhibitory and co-stimulatory receptors that are known to induce T cell dysfunction and which is possibly associated with loss of viral control in the majority of acutely HCV infected patients. (nature.com)
  • Her work focuses on the role of co-stimulatory and co-inhibitory receptors in primary human Treg function in health and disease. (ucl.ac.uk)
  • Co-stimulatory and co-inhibitory receptors are crucial to determine functional outcomes upon activation. (ucl.ac.uk)
  • This event also provides a co-stimulatory signal leading to the production of IL-2 and T- cell activation. (wikipathways.org)
  • Here, we present data for the new PathHunter® Checkpoint assays that target clinically relevant co-inhibitory and co-stimulatory checkpoint receptors and measure receptor activation and signaling, using the industry-validated Enzyme Fragment Complementation (EFC) technology. (discoverx.com)
  • In, "A TIGIT-based chimeric co-stimulatory switch receptor improves T cell anti-tumor function," Hoogi et al . (sitcancer.org)
  • In contrast to targeting co-inhibitory checkpoint inhibitors such as PD-1/PD-L1, the new strategy is to include a co-stimulatory agonist. (pharmaceutical-technology.com)
  • ZAP70 induces activation of LAT (Linker for Activation of T-Cells), an integral membrane adaptor protein which further binds to GADS (Growth Factor Receptor-Bound Protein-2-Related Adaptor Protein-2), SLP76 (SH2 Domain-Containing Leukocyte Protein-76), and ITK (IL-2 inducible T-cell kinase). (wikipathways.org)
  • Another FcR is expressed on multiple cell types and is similar in structure to MHC class I . This receptor also binds IgG and is involved in preservation of this antibody. (wikipedia.org)
  • PD-L1, binds to PD-1, Src family kinases phosphorylate the ITIM motif, resulting in the recruitment of SH2-domain containing phosphatases, SHP-1 and SHP-2, which are involved in inhibiting the T-cell response. (discoverx.com)
  • This comprehensive phenotypic study confirms TIGIT together with PD-1 as a discriminatory marker of dysfunctional HCV-specific CD4+ T cells. (nature.com)
  • This also provides a proof of concept for developing assays for other therapeutically relevant checkpoint receptors, such as TIGIT and CD47. (discoverx.com)
  • NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
  • Nascent transformed cells elicit NK cell activation and are eliminated. (frontiersin.org)
  • The guanine nucleotide exchange factor VAV1 is required for T cell receptor (TCR) signaling and activation of T cells. (sciencemag.org)
  • The activation of T cells requires the guanine nucleotide exchange factor VAV1. (sciencemag.org)
  • In sum, activation of MSCs with inflammatory stimuli turns these cells into suppressive cells capable of mediating adaptive regulation of proinflammatory pathogenic T-cells. (frontiersin.org)
  • T cell activation is initiated when antigen is presented to the T cell receptor (TCR) complex by MHC class I or II on an antigen-presenting cell. (jci.org)
  • Following T cell activation, the B7-1-B7-2 interaction with CTLA-4, expressed on activated T cells, leads to down-regulation of T cell activation, whereas stimulation of the TCR alone leads to T cell clonal anergy. (dana-farber.org)
  • Circulating immune complexes and cell-bound immunoglobulins present in normal human sera represent a potential stimulus for inadvertent DC activation in the steady state and during autoimmunity. (pnas.org)
  • These data suggest an approach for modifying this balance to enhance immunity to immune complexes and antibody-coated tumor cells and to silence DC activation by immune complexes in autoimmune states. (pnas.org)
  • This complex participates in T-cell activation upon the presentation of the antigen peptide (derived from the foreign antigen) bound to the MHC (Class I and Class II) residing on antigen-presenting cells (APCs), including dendritic cells, macrophages and B cells. (wikipathways.org)
  • The activated Src kinases phosphorylate ITAMs (Immune receptor tyrosine-based activation motifs) present on CD3γ, δ, ε and ζ chain. (wikipathways.org)
  • ZAP70 also activates IKKs via the CARD11 (Caspase recruitment domain family, member 11) -BCL10 (B-Cell CLL/lymphoma-10)-MALT1 (Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene-1) complex and MAP3K (activated by PKCθ) which in turn relieve NF-κB of IκB (NF-kappa-B inhibitor beta) and allow its nuclear translocation and transcriptional activation. (wikipathways.org)
  • It is speculated that the costimulatory regulation of T cells by B7S1 is influenced by the activation status of B cells. (thermofisher.com)
  • Mesenchymal stem cells (MSCs) have been considered as an invaluable cell type, owing to their unique immunomodulatory properties, which makes them desirable for application in transplant settings, where hyper-activation of the immune system is evident. (springer.com)
  • CTLA4 is an essential negative regulator of T-cell activation. (thermofisher.com)
  • Expression of CTLA4 is up-regulated within 1 hour following T-cell activation, where it is trafficked by reorganization of the microtubule-organizing center to the cell surface. (thermofisher.com)
  • The activation of T-cells by Antigen-MHC-II complex carried on antigen presenting cells is a complex process involving a cascade of events, the first of which is phosphorylation of the PTKs (Protein Tyrosine Kinases) belonging to the Src and SYK ZAP70 (Zeta-Chain-Associated Protein Kinase) families. (thermofisher.com)
  • Initiation of T-cell activation is mediated by phosphorylation of the ITAMs (Immunoreceptor Tyrosine-based Activation Motifs) on the TCR-CD3 complex by Lck (attached to CD4 or CD8), and Fyn, both of which are members of the Src family of kinases. (thermofisher.com)
  • The activation or inhibition of NK cells is regulated by several membrane receptors, commonly designated as NK cell receptors (NKR). (bmj.com)
  • This results in PD-1 activation and SHP-1 recruitment to the PD-1 receptor, bringing together the two EFC fragments and generating a light signal. (discoverx.com)
  • B7‑H3 was also reported to play an inhibitory role on T-cell activation. (rndsystems.com)
  • CONCLUSIONS Our data indicate substantial activation of both CD4+ and CD8+ lung T cells in sarcoidosis. (bmj.com)
  • Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. (pubmedcentralcanada.ca)
  • Accumulation of a functionally impaired subpopulation of CD20 hi CD27 - CD21 lo tissue-like memory B cells in the peripheral blood of HIV-viremic individuals is a consequence of persistent HIV viremia and is likely induced by chronic immune activation ( 1 , 2 ). (pubmedcentralcanada.ca)
  • Inhibitory receptors containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) are differentially expressed during lymphocyte activation and differentiation. (pubmedcentralcanada.ca)
  • Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. (sciencemag.org)
  • Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. (sciencemag.org)
  • Thus, at least under conditions of short-term stimulation, Tim-3 can augment T-cell activation, although this effect can be blocked by the inclusion of an agonistic antibody to Tim-3. (asm.org)
  • Recently, it has been shown that IFN-γ-mediated clearance of hepatitis B virus (HBV) can occur in the liver of infected chimpanzees before the accumulation of T cells and that this could be a consequence of NK cell activation ( 16 ). (pubmedcentralcanada.ca)
  • Our study addresses a fundamental immunological mechanism for the control of T cell activation during antigen presentation, TCR down‐modulation. (embopress.org)
  • This finding expands the role of PD‐L1 in immune regulation to a critical step in T cell activation. (embopress.org)
  • In addition activation and T cell markers were used for the identification of TCD4 + and TCD8 + subpopulations. (biomedcentral.com)
  • Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. (biomedcentral.com)
  • Combinations with other immunomodulatory mAb that block T-cell checkpoint blockade receptors such as CTLA-4 and PD-1 are also promising. (aacrjournals.org)
  • On December 12, 2013 he was announced as a recipient for the prestigious Breakthrough Prizes in Life Sciences for the discovery of T cell checkpoint blockade as effective cancer therapy. (ucsf.edu)
  • Further studies showed that PD-L1 is highly expressed by many solid tumors/hematological malignancies, and that blockade of PD-L1 enhances killing of PD-L1 positive targets by CD8 T cells. (dana-farber.org)
  • FcγRIIb blockade of DCs loaded with tumor cells led to increased tumor-specific T cell immunity without the need for exogenous stimuli other than human plasma. (pnas.org)
  • Combination blockade also synergistically increases Teff-to-myeloid-derived suppressor cell ratios within B16 melanomas. (pnas.org)
  • Neutralization of inhibitory receptors, or "checkpoint blockade," can reverse T cell exhaustion and lead to beneficial prognoses in experimental and clinical settings. (asm.org)
  • Moreover, the gamma interferon (IFN-γ) response of CD8 but not CD4 T cells is significantly reduced during secondary infection with virulent strains, suggesting that checkpoint blockade may reduce disease severity. (asm.org)
  • To determine the effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β (TCRβ) genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes. (sciencemag.org)
  • CTLA-4 blockade in patients with metastatic castration-resistant prostate cancer and metastatic melanoma resulted in both expansion and loss of T cell clonotypes, consistent with a global turnover of the T cell repertoire. (sciencemag.org)
  • Together, these results suggest that CTLA-4 blockade induces T cell repertoire evolution and diversification. (sciencemag.org)
  • It contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. (beckman.com)
  • Siglec-G is often referred to as the murine paralog of human Siglec-10 Like most but not all other Siglecs, Siglec-10 bears an ITIM (Immunoreceptor tyrosine-based inhibitory motif) within its cytoplasmic domain. (wikipedia.org)
  • The PD1.3 monoclonal antibody recognizes T cells, activated CD4 and CD8 positive cells and activated B cells. (beckman.com)
  • In embryonic stem cells, FBXL10 is critical for targeting PRC1 to CpG islands and regulating gene expression during differentiation. (cellsignal.com)
  • PAX5 is a member of the highly conserved paired-box (PAX) domain family of transcription factors necessary for many types of cell differentiation. (haematologica.org)
  • PAX5 is the only PAX family member expressed within the hematopoietic system, and its expression is restricted to certain stages along the B-cell differentiation pathway. (haematologica.org)
  • Moreover, CCRL1(-/-) mice have no major perturbations in T-cell populations at different stages of thymic differentiation and development, and have a similar rate of thymocyte migration into the blood. (diva-portal.org)
  • To assess whether activated MSC can modulate adaptive immunity, MSCs were pulsed with islet auto-antigen (GAD65) peptide to stimulate GAD65-specific T-cells. (frontiersin.org)
  • Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. (rupress.org)
  • These agents are commonly called "immune checkpoints" because they block negative regulators of T cell immunity. (biovision.com)
  • The natural killer (NK) cell is a critical part of anti-tumor immunity. (medsci.org)
  • Natural killer (NK) cells are a critical part of innate immunity, acting as the main defense against the spread of cancer [ 3 ]. (medsci.org)
  • The CMV life strategy is to integrate DNA into the genome of the host cells and escape the mechanism of natural immunity. (wikipedia.org)
  • The FcγR system represents a balance of activating and inhibitory receptors that determines the outcome of immune complex-mediated inflammation and immunity ( 24 ). (pnas.org)
  • These are all settings where cellular immunity is important, and thus we wish to map the detailed phenotypes and functions of the immune cells involved. (stanford.edu)
  • Defining the role of NK cells in viral immunity. (stanford.edu)
  • B7-H4 (B7x, VTCN1) a costimulatory protein which is reported to function as a negative regulator of T-cell mediated immunity. (thermofisher.com)
  • Overexpression of B7-H4 is associated with certain malignancies, including ovarian and breast cancer, which may be a mechanism by which tumor cells suppress T cell immunity and facilitate tumor progression. (thermofisher.com)
  • Importantly, these results suggest that one mechanism whereby HCV can alter host defenses and innate immunity is via the early inhibition of IFN-γ production by NK cells. (pubmedcentralcanada.ca)
  • The current paradigm of receptor-mediated signal transduction suggests two explanations ( 8 , 9 ). (jimmunol.org)
  • Not unexpectedly, the Toll interleukin receptor domains of the TLR, IL1, and IL18 receptors activate similar signal transduction cascades. (bmj.com)
  • T cell receptor (TCR) down‐modulation after antigen presentation is a fundamental process that regulates TCR signal transduction. (embopress.org)
  • This process limits TCR signal transduction and prevents T cell hyperactivation after antigen‐presentation by dendritic cells. (embopress.org)
  • Abs or their recombinant fragments against surface receptors of the Ig superfamily can induce or block the receptors' native function depending on whether they induce or prevent the assembly of signalosomes on their cytoplasmic tails. (jimmunol.org)
  • Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. (biomedcentral.com)
  • Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. (wikipedia.org)
  • PD-1), Tim-3 does not contain any obvious inhibitory signaling motifs. (asm.org)
  • ABSTRACT Natural killer (NK) cells are key players in the immune response to viruses. (who.int)
  • CD80 is expressed by macrophages, dendritic cells and activated B cells. (fishersci.com)
  • Their activity stimulates phagocytic or cytotoxic cells to destroy microbes , or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity . (wikipedia.org)
  • Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. (sciencemag.org)
  • NK cells play an important role in the early innate host defense against a number of pathogens. (pubmedcentralcanada.ca)
  • a ǀ Dendritic cell (DC) priming can be accomplished in multiple ways. (nih.gov)
  • a ǀ Multiple targeted agents affect dendritic cell (DC)-mediated priming of T cells. (nih.gov)
  • Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. (bmj.com)
  • A schematic of the interactions between a CD4 T cell (left) or CD8 T cell (right) and its activating dendritic cell. (brainscape.com)
  • A scanning electron micrograph (left) shows the binding of a T cell (artificially colored yellow) and dendritic cell (artificially colored blue). (brainscape.com)
  • Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. (frontiersin.org)
  • Our results indicate that coexpression of LAG-3 and 4-1BB characterize dysfunctional T cells within tumors, and that targeting these receptors has therapeutic utility. (rupress.org)
  • Potential therapeutic use of memory cells is vaccination based on induction of memory T cells in the periphery that will be capable of effectively and immediately attacking the pathogen. (wikipedia.org)
  • One key inhibitory checkpoint receptor that is the target of several therapeutic agents in the clinic is programmed cell death 1 (PD-1). (discoverx.com)
  • In particular, these highlighted articles show how insight into the interplay between malignant cells and the immune system can unlock new therapeutic strategies and diagnostic tools. (sitcancer.org)
  • Ultimately, inhibiting or agonizing receptors on this subpopulation could have therapeutic relevance. (biomedcentral.com)
  • The classes of FcR's are also distinguished by the cells that express them (macrophages, granulocytes, natural killer cells, T and B cells) and the signalling properties of each receptor. (wikipedia.org)
  • [10] FcαRI is found on the surface of neutrophils , eosinophils, monocytes, some macrophages (including Kupffer cells ), and some dendritic cells . (wikipedia.org)
  • BACKGROUND The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. (bmj.com)
  • In early disease there is a mononuclear cell alveolitis dominated by activated CD4+ (helper/inducer) T cells and macrophages. (bmj.com)
  • The cell subsets studied were CD4+ and CD8+ T cells in peripheral blood and BAL fluid, as well as peripheral blood monocytes and macrophages. (bmj.com)
  • In this study, we report that murine CMV drastically reduces the expression of several SLAM family receptors at the cell surface of infected macrophages, most likely as part of its immunoevasion mechanisms. (prolekare.cz)
  • T and NK cells express several members of the TNF receptor (TNFR) family specialized in delivering a costimulatory signal on their surface. (aacrjournals.org)
  • The role of the costimulatory members of the TNFR family seems to be related to signaling. (aacrjournals.org)
  • T and NK cells express a panoply of cell surface members belonging to the TNFR family ( Fig. 1 and Table 1 ). (aacrjournals.org)
  • Cell surface-attached costimulatory members of the TNF and TNFR superfamilies. (aacrjournals.org)
  • Schematic representation of the sites and cells on which agonist anti-CD137 mAbs act as example of TNFR mAb mechanism. (aacrjournals.org)
  • Programmed Death-1 (PD-1) is one of the coinhibitory receptors, with notably Cytotoxic T Lymphocyte Antigen 4 (CTLA4) and CD272 (BTLA). (beckman.com)
  • When given a lethal secondary infection, CD8 and CD4 T cells upregulate several coinhibitory receptors, including PD-1, TIM-3, 4-1bb, and CTLA-4. (asm.org)
  • It is a type I membrane glycoprotein whose extracellular region contains three scavenger receptor cysteine-rich (SRCR) domains. (selectscience.net)
  • It is not constitutively expressed but is upregulated in a manner dependent on TCR stimulation, such that greater stimulation produces more CTLA4 at the cell plasma membrane (Ref. 5 & 4). (thermofisher.com)
  • At the cell membrane, CTLA4 undergoes dimerization, and each CTLA4 dimer can bind two independent B7-1/B7-2 homodimers, forming a linear zipper-like structure between B7-1/B7-2 and CTLA-4 homodimers (Ref. 6 & 7). (thermofisher.com)
  • CD161 is a C-type lectin-like membrane receptor and is also known as NKR-P1A. (prolekare.cz)
  • In this study, PD-L1 protein extracted from the cell membrane was found to be downregulated in OSC-20 cells compared with OSC-19 cells, despite a higher PD-L1 expression in the total cell lysate of the OSC-20 compared with the OSC-19 cells. (spandidos-publications.com)
  • VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. (rupress.org)
  • For example, B7h on APCs stimulates T cells by binding ICOS (inducible costimulator), and PD-L1 and PD-L2 inhibit T cells by binding PD-1. (blackwaterpaddleandpedal.com)
  • Unraveling the principles of WAT immune cell regulation and their amenability to change by host-microbiota interactions may lead to a conceptual leap forward in our understanding of metabolic physiology and disease. (europa.eu)
  • The combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. (nature.com)
  • Despite its well-known functions it has been recently reported that NK cells are also involved in the regulation of the adaptive immune response. (bmj.com)
  • We provide evidence that this occurs via Casitas B‐lymphoma (Cbl)‐b E3 ubiquitin ligase up‐regulation in CD8 T cells. (embopress.org)
  • Measured by its ability to inhibit anti-CD3 antibody induced IL-2 or IFN-gamma secretion by human T cells. (rndsystems.com)
  • It is defined by poor T-cell effector function, sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T- cells. (google.com)
  • Here, we show that CCRL1 is expressed within the thymic cortex, predominantly by MHC-II(low)CD40(-) cortical thymic epithelial cells and at the subcapsular zone by a population of podoplanin(+) thymic epithelial cells in mice. (diva-portal.org)
  • ICOS produced in Sf9 Baculovirus cells is a single, glycosylated polypeptide chain containing 362 amino acids (21-140a.a.) and having a molecular mass of 40.8kDa. (prospecbio.com)
  • However, it should be noted that many molecular players are acting in a structured and concerted fashion at the synapse including receptors, signaling adaptors, cytoskeletal components, and the distribution of lipids in the interacting plasma membranes ( 2 ). (aacrjournals.org)
  • Signaling by means of this receptor leads to recruitment and phosphorylation of an SH2 domain containing inositol polyphosphate 5′ phosphatase that regulates signaling by activating receptors ( 11 , 12 ). (pnas.org)
  • This symposium will discuss the importance of cellular senescence and immune signaling in IPF as well as the roles of endothelial cells and alveolar epithelial cells, which are emerging as key drivers of disease. (nyas.org)
  • But in the context of an additional negative-signaling protein, such as PP2A, SHP1 and SHP2 would be dominant by interfering with T-cell function (Ref. 8, 6 & 1). (thermofisher.com)
  • Signaling through CTLA4 inhibits IL-2 mRNA production and inhibits cell cycle progression. (thermofisher.com)
  • For a quick summary, see our T Cell Co-Signaling Pathway . (rndsystems.com)
  • Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR −/− ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. (asm.org)
  • Although IFN-α/β receptor knockout (α/βR −/− ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. (asm.org)
  • Although inhibitory receptors are critical for the normal function of the immune system, their persistent expression can result in decreased cell function, anergy, and exhaustion, as has been observed in persistent viral infections and autoimmune diseases ( 4 - 6 , 10 ). (pubmedcentralcanada.ca)
  • There is compelling clinical and experimental evidence to suggest that natural killer (NK) cells play a critical role in the recognition and eradication of tumors. (frontiersin.org)
  • However, a class of important immune-modulators is conspicuously absent: agents that utilize the power of innate immune cells to eradicate tumors. (frontiersin.org)
  • Notably, an estimated 60-69% of triple negative breast cancers (with absence of oestrogen receptor (ER) progesterone receptor (PR) as well as nonamplified HER2) are reported to have a defect in DNA repair, with features in common with BRCA1/2 mutated tumors described as "BRCAness" [ 5 , 6 ]. (hindawi.com)
  • Immunotherapies that block co-inhibitory receptors such as PD-1 and CTLA-4 are showing unprecedented efficacy in the treatment of some tumors, and have generated interest in the characterization of additional immunotherapy targets that may broaden the number of patients who can be helped by these drugs. (aacrjournals.org)
  • Surgical resection is one of the primary treatments for solid tumors, but the dissemination of tumor cells into the blood and lymphatic systems inevitably occurs during surgery. (medsci.org)
  • used a three-dimensional, collagen-fibrin gel system to investigate the effects of CD8 + T cells on cocultured melanoma cells excised from mouse tumors. (sciencemag.org)
  • These receptors are now recognized as promising immunotherapy targets for the treatment of many cancers and autoimmune diseases. (aacrjournals.org)
  • She established methods to knock out receptors in primary human Tregs via CRISPR-Cas and applied the technology to elucidate the role of the TNF receptors in Treg function and survival. (ucl.ac.uk)
  • Phenotypic studies examining Treg frequency in peripheral blood have showed similar proportions of these cells in patients who developed TB-IRIS and those who did not. (bloodjournal.org)
  • They examined tumor-infiltrating Tregs and CD3+ T cells using quantitative DNA demethylation analysis (epigenetic qPCR) and by immunohistochemistry, and peripheral blood Treg proportions measured by flow cytometry. (medicalxpress.com)
  • An important class of innate immune cells that play a critical role in mediating the antitumor immune response is the natural killer (NK) cell. (frontiersin.org)
  • Immune response against CMV is primarily provided by CD8 + T cells which recognize viral fragments in MHC class I complex on the surface of infected cells and destroy these cells. (wikipedia.org)
  • Recently, we have cloned two novel members of the B7 gene family, which bind to receptors expressed on activated T cells and further regulate the development of an immune response. (dana-farber.org)
  • Tumor protection was associated with a systemic immune response with memory and antigen specificity and required CD4(+) cells and CD8(+) T cells. (nih.gov)
  • there are still conflicts in results about their respective roles in initiation or sustaining of the T cell immune response. (fishersci.com)
  • Analysis of the immune response revealed increased virus-specific antibody levels in Ceacam1(-/-) mice, while the magnitude of the T cell-mediated antiviral immune response was reduced. (uni-muenchen.de)
  • suggesting B7-H4 is important in the fine tuning of the T-cell mediated immune response. (thermofisher.com)
  • The rationale behind targeting immune receptors is to prevent cancer-mediated immune suppression and thereby allow a normalized immune response against cancer. (pharmaceutical-technology.com)
  • The ability to quickly produce large amounts of IFN-γ is believed to be a key function of NK cells in the innate immune response. (pubmedcentralcanada.ca)
  • The early production of IFN-γ by NK cells enable them to skew the adaptive immune response to a Th1 inflammatory response. (pubmedcentralcanada.ca)
  • The possibility that HCV might be able to alter NK cell functions and thus the innate immune response has not been fully explored. (pubmedcentralcanada.ca)
  • Therefore, it is possible that the parasite exploits host cell apoptosis to evade the immune response. (biomedcentral.com)
  • We therefore suggest that the influenza virus use a novel mechanism for the inhibition of NK cell activity. (jimmunol.org)
  • We have recently demonstrated that the viral hemagglutinin (HA) 3 protein of influenza virus and the HA-neuraminidase (HN) protein of Sendai virus (SV) can interact with both the NKp44 and NKp46 receptors and that this interaction leads to increased killing that can overcome the class I MHC-mediated inhibition ( 4 , 5 ). (jimmunol.org)
  • To date, melanoma and non-small cell lung cancer (NSCLC) are the two tumor types for which the use of immune checkpoint inhibition has received Food and Drug Administration approval. (aspetjournals.org)
  • In contrast, the inhibitory FcγR contains an immune tyrosine inhibitory motif. (pnas.org)