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.
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.
Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.
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)
Endogenous superantigens responsible for inducing strong proliferative responses in T-cells in mixed lymphocyte reactions (see LYMPHOCYTE CULTURE TEST, MIXED). They are encoded by mouse mammary tumor viruses that have integrated into the germ line as DNA proviruses (MINOR LYMPHOCYTE STIMULATORY LOCI).
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
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.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
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)

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

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

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

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Multiple sclerosis. (5/15)

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

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

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

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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 ...
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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 ...
"Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1 ... diversity down-regulation of CD28 costimulatory molecules cytotoxic activity of Natural Killer T cells (NKTs) decreases due to ... T cells are not the only immune cells affected by aging: Hematopoietic stem cells (HSC), which provide the regulated lifelong ... increase in the expression of the inhibitory (KIR, NKG2C, etc.) receptors of NK cells reduction of cytotoxic activity due to ...
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 ...
"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 ...
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 ...
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 ...
... 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 ...
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. ...
The receptor is an immune checkpoint and together with other inhibitory receptors including programmed cell death protein 1 (PD ... Rodriguez-Manzanet R, DeKruyff R, Kuchroo VK, Umetsu DT (May 2009). "The costimulatory role of TIM molecules". Immunological ... Later, the expression was detected in Th17 cells, regulatory T-cells, and innate immune cells (dendritic cells, NK cells, ... myeloid cells (monocytes, macrophages, DC, mast cells, NK cells) or various cells in different tumor types. ...
... and contributes to their inhibitory function. T cell activation through the T cell receptor and CD28 leads to increased ... CTLA-4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and ... and have low CTLA-4 protein expression in T regulatory cells, hyperactivation of effector T cells, low switched memory B cells ... CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. In November 1995, the labs of ...
12 This works to repress immune responses by binding to the inhibitory FC receptor, FCγRIIB. Furthermore, HCV's core protein ... Knockout mice for FGL2 have T cells that are hyperproliferative. sFGL2 is capable of inhibiting the proliferation of T cells ... by preventing NF-κB translocation to the nucleus and subsequent expression of the co-stimulatory molecule CD80 and major ... can be inducibly secreted by Foxp3+ CD4+ CD25+ T regulatory cells (Tregs). Such Treg cells play a vital role in dampening the ...
... peptide complex on a dendritic cell interacts with the receptor on a T helper cell, CD80 is up-regulated, licensing the ... Both CD80 and CD86 interact with costimulatory receptors CD28 and CTLA-4 (CD152). CD80 is a member of the B7 family, which ... This illustrates that inhibitory interaction with CTLA-4 is predominant. CD80 binds to CD28 and CTLA-4 with lower affinity and ... including B-cells, monocytes, or T-cells, but most typically at antigen-presenting cells (APCs) such as dendritic cells. CD80 ...
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 ...
... 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 ... December 2004). "Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential ... The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with ... PD-L1 is expressed on T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells. ...
NK cell activity is mediated by a variety of cell surface receptors with stimulatory and inhibitory activity. Under normal ... Co-stimulation regulates responsiveness of T cells and NKG2D is one of well-documented co-stimulatory molecules for T cells., ... T cells, γδ T cells, activated CD8+ αβ T cells and activated macrophages. In humans, it is expressed by NK cells, γδ T cells ... NKG2G is a key stimulatory cell surface receptor. A low expression of the receptor is observed already in the early NK cells ...
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. ...
... 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 ...
"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 ...
... 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 ...
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 ...
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 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 ...
... 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. ... May 2013). "TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen- ... June 2014). "Human somatic cell nuclear transfer using adult cells". Cell Stem Cell. 14 (6): 777-80. doi:10.1016/j.stem.2014.03 ...
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 ...
"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 ...
October 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". The Journal of Biological ... a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". Journal of ... October 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". The Journal of Biological ... SLP-76 is also important in natural killer (NK) cells, in the signaling pathways of the NK cell receptors (NKRs). The SH2 ...
... 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 ...
... which binds and stimulates the B cell surface receptor CD40. TFH cell-dependent paracrine activation of B cell CD40 results in ... Therefore, TFR cells are a uniquely inhibitory influence during a germinal center reaction. While TFH cells are found primarily ... "The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and ... Pre-TFH cells are functionally very similar to other TFH cells in facilitating germinal center B cell reactions however, in ...
... 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 ... Trogocytosis (Greek: trogo; gnaw) is when a cell nibbles another cell. It is a process whereby lymphocytes (B, T and NK cells) ...
For optimal T-cell activation, T-cell receptor ligation to peptide-MHC complexes combined with costimulatory (i.e., CD28) ... However, inhibitory (i.e., CTLA-4 and PD-1) molecules (so-called immune checkpoints) on T cells play a crucial role in ... PD-1 (CD279), also a homolog of CD28, is a receptor induced on the cell surface of activated T cells, B cells and myeloid cells ... CTLA-4 (CD152), a homolog of the costimulatory molecule CD28, is a receptor for CD80 and CD86, and is essential for T-cell ...
... activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory ... Upon activation, coinhibitory checkpoints, including programmed cell death protein 1 (PD1), become induced to regulate T ... cells. PD1 has an essential role in b … ... engagement of the T cell receptor and positive costimulatory ... The diverse functions of the PD1 inhibitory pathway Nat Rev Immunol. 2018 Mar;18(3):153-167. doi: 10.1038/nri.2017.108. Epub ...
Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sa... ... Regulation of T-cell function is orchestrated by costimulatory and coinhibitory pathways. Inhibitory receptors, such as ... CM = central memory T cells; EM = effector memory T cells; N = naive T cells; TEM = terminal effector memory T cells. ... T cells, as well as on sarcoidosis APCs, specifically monocytes, B cells, and CD11c+ cells that could include dendritic cells ...
Natural killer cell populations in Egyptians infected with hepatitis C virus ... More focused research on this cell population with its different stimulatory, co-stimulatory and inhibitory receptors might ... Some T cells are known to express NK cells receptors (NKRs) and mediate functions of both T cells and NK cells [13]. Studies ... Negative regulation of NK cell activities by inhibitory receptor CD94/NKG2A leads to altered NK cell-induced modulation of ...
Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, ... Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, ... EU PEGS] Ready-to-Use Cell-Based Assays to Enable Immunotherapy Drug Development for Checkpoint Receptors ... Tools & Resources / Document Resource Library / Documents / [EU PEGS] Ready-to-Use Cell-Based Assays to Enable Immunotherapy ...
... some co-receptors can dampen Ca2+ signaling and inhibit T cell activation. Immune checkpoint therapies block inhibitory co- ... T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an ... to increase T cell Ca2+ signaling and promote T cell survival. Similar to CTLA-4 and PD-1, the co-receptor CD5 has been known ... Though much is known about the role of CD5 in B cells, recent research has expanded our understanding of CD5 function in T ...
NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. ... The provision of proper costimulatory receptor activity and cytokine stimuli, along with the repression of inhibitory ... tumor cells were killed by antigen-specific T-cell receptor (TCR) transgenic CD8 T cells or activated NK cells. Immunogenic ... Scavenger receptor class B type I (SR-B1) is the receptor for ApoA-I and is expressed on the surface of tumor cells. SR-B1 can ...
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. These findings ... Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell ... Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally ...
GenScript offers a large product portfolio of GPCR and ion channel stable cell lines used in cell-based assay for compound ... including Fc gamma receptors, neonatal Fc receptor, G protein-coupled receptors, co-inhibitory and co-stimulatory immune ... Fc Receptor Cell Lines Flyer Fc Receptor Cell Lines Flyer Cell line product catalog including brief introductions, product list ... Stable Cell Lines Brochure Stable Cell Lines Brochure Cell line product catalog including brief introductions, product list and ...
Moreover, reporter activation was detectable upon interaction with HLA-E+ .221-AEH cells, as well as with .221 cells incubated ... which displays high surface levels of the activating CD94/NKG2C NK cell receptor, together with additional distinctive ... Engagement of the receptor by solid-phase bound CD94- or NKG2C-specific monoclonal antibodies (mAbs) triggered Luc expression. ... Engagement of the receptor by solid-phase bound CD94- or NKG2C-specific mAbs triggered Luc expression. ...
Inhibitory T-Cell. Receptors, Inhibitory T-Lymphocyte. Receptors, Inhibitory, T-Cell. T-Cell Receptors, Costimulatory. T-Cell ... Receptors, Inhibitory T-Cell Receptors, Inhibitory T-Lymphocyte Receptors, Inhibitory, T-Cell T-Cell Receptors, Inhibitory T- ... Inhibitory T-Cell Receptors. Inhibitory T-Lymphocyte Receptors. Receptors, Costimulatory T-Cell. Receptors, Costimulatory T- ... Costimulatory and Inhibitory T-Cell Receptors Entry term(s). Costimulatory and Inhibitory T Cell Receptors Costimulatory and ...
CD36 and CD51 were identified as the receptors on DCs responsible for this inhibitory effect.[42] These same receptors were ... Impairment of dendritic cell function. Dendritic cells (DC) are usually the first cells of the immune system to encounter ... Urban et al (1999) first showed that P. falciparum infected erythrocytes could prevent up-regulation of MHC Class II and co-stimulatory ... IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses. Cell Immunol 2002;215 ...
Costimulatory and Inhibitory T-Cell Receptors Medicine & Life Sciences 100% * Immunological Synapses Medicine & Life Sciences ... During T cell activation, T cell receptors (TCR) cluster at the center of the T cell/antigen-presenting cell interface forming ... N2 - During T cell activation, T cell receptors (TCR) cluster at the center of the T cell/antigen-presenting cell interface ... AB - During T cell activation, T cell receptors (TCR) cluster at the center of the T cell/antigen-presenting cell interface ...
... or co-stimulatory CD40 molecules (44). TLRs could act as adaptor receptors, influencing the responses induced by MHC class II ... mediated inhibitory signaling pathway, involving FcγRγ- and ERK-mediated recruitment of SHP-1 that suppresses DC maturation and ... A and B, CD4+ T-cell tolerance in vivo. OT-II CD4+ T cells were transferred i.v. into naïve C57BL/6 mice (5 × 106 cells per ... A and B, CD4+ T-cell tolerance in vivo. OT-II CD4+ T cells were transferred i.v. into naïve C57BL/6 mice (5 × 106 cells per ...
Figure 3: Co-stimulatory and co-inhibitory molecules set thresholds for T-cell activation.. ... A large and diverse set of recognition molecules - antibodies (produced by B cells) and T-cell receptors - mediate adaptive ... Dendritic cells. These cells present antigen to T cells, and stimulate cell proliferation and the immune response. ... Effector T cells fall into two classes - CD8+ killer or cytotoxic T cells, which destroy infected cells, and CD4+ or helper T ...
CTLA4 attenuates T cell activation by inhibiting co-stimulatory signal via CD28 and transmitting inhibitory signals to T cells ... To avoid over-reactivation, effector T cell response also require suppression signals generated upon co-inhibitory receptor- ... Co-stimulatory receptor-ligand interactions that help amplify effector T cell responses include CD28-CD80, 4-1BB (also known as ... T cells in tubercular pleural fluid, with biased usage of T cell receptor Vβ chains. Infect Immun. 2011;79(8):3358-65. ...
Antigen-Presenting Cells 74% * T-Lymphocytes 65% * Costimulatory and Inhibitory T-Cell Receptors 58% ... Structural basis of inducible costimulator ligand costimulatory function: Determination of the cell surface oligomeric state ... T Cell Immunoglobulin Mucin-3 Crystal Structure Reveals a Galectin-9-Independent Ligand-Binding Surface. Cao, E., Zang, X., ... The interchain disulfide linkage is not a prerequisite but enhances CD28 costimulatory function. Lazar-Molnar, E., Almo, S. C. ...
The discovery that blocking an inhibitory immune receptor restores T cell function in HIV sheds light on immune dysfunction. ... Programmed death I (PD-1), an inhibitory receptor on immune system cells, has long been known to play an important dual role in ... "Programmed Death-1 Ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses," Immunity ... The discovery that blocking an inhibitory immune receptor restores T cell function in HIV sheds light on immune dysfunction.. ...
D12.776.543.750.705 Receptors, Immunologic .. D12.776.543.750.705.222 Costimulatory and Inhibitory T-Cell Receptors .. D12.776. ... gp39 Antigen, T-Cell .. T-Cell gp39 Antigen .. gp39 Antigen, T Cell .. Antigens, CD154 .. CD154 Antigens .. Tumor Necrosis ... T-B Cell Activating Molecule .. TNF Superfamily, Member 5 .. ...
Transplantation is the act of transferring cells, tissues, or organs from one site to another. The malfunction of an organ ... the second by a costimulatory receptor/ligand interaction on the T cell/APC surface. Of the numerous costimulatory pathways, ... The recognition is mediated by various NK inhibitory receptors triggered by specific alleles of MHC class I antigens on cell ... In this stage, the CD4 and CD8 T cells, via their T-cell receptors, recognize the alloantigens expressed on the cells of the ...
... patients showed a higher expression of costimulatory molecules while a diminished expression of the inhibitory receptors, ILT2 ... Dendritic cells (DCs) and regulatory T cells (Tregs) play an essential role in myocarditis. However, a particular DC phenotype ... Cell viability decreased in the presence of exosomes from infarcted patients, while incubation of H9c2 cells with exosomes from ... Altered Phenotype of Circulating Dendritic Cells and Regulatory T Cells from Patients with Acute Myocarditis. ...
Costimulatory and Inhibitory T-Cell Receptors. *Immunophilins. *Integrins. *Platelet Membrane Glycoproteins. *Receptors, ... Cell division cycle 7 kinase is a negative regulator of cell-mediated collagen degradation. Am J Physiol Lung Cell Mol Physiol ... Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell. 2014 Feb 13; ... Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180. Cancer ...
Co-stimulatory (TNFRSF4 and TNFRSF18) and co-inhibitory (LAG3) receptors were similarly upregulated in blinatumomab-activated T ... We found that CD8+ effector memory T cells, CD4+ central memory T cells, naïve T cells, and regulatory T cells were activated ... Particularly, B-ALL cell expression of TNFSF4, which encodes the ligand of T cell co-stimulatory receptor TNFRSF4, was found ... In total, the transcriptome of 17,920 single T cells from the cell line model and 2271 single T cells from patient samples were ...
The B and T lymphocyte attenuator (BTLA) appears to act as a negative regulator of T cell activation and growth. BTLA ... IMGT Colliers de Perles and IgSF domain standardization for T cell costimulatory activatory (CD28, ICOS) and inhibitory (CTLA4 ... Crystal structure of the soluble human 55 kD TNF receptor-human TNF β complex: implications for TNF receptor activation. Cell ... For example, BTLA in C57BL/6 mice is expressed on T cells, B cells, macrophages, NK cells, and dendritic cells (2). In contrast ...
... characteristics and underlying mechanisms of co-inhibitory and co-stimulatory receptors on cancer-specific cytotoxic T cells ... of HLA-E and its inhibitory receptors CD94/NKG2a and exploitation of this machinery by cancer to inhibit anti-tumor T cell ... Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses. Journal ... 2. Importance of self-sustain, highly energetic CD103+ tissue resident memory T cells in anti-tumor responses ...
... co-stimulatory/ co-inhibitory receptors on T cells must bind B7 ligand family expressed on APCs to regulate situation of T cell ... CD19 BCMA CD3 proteins IL-2 and IL-2 receptor proteins Inspiring Target: Interleukin 4 Receptor New IL-6 and IL-6 receptor ... T cell activation is regulated by the innate immune system through positive and negative costimulatory molecules. Members of ... Immobilized cell surface PD-1 (5x104 of cells per well) can bind Human PD-L1, Fc Tag (Cat. No. PD1-H5258) with an EC50 of 0.029 ...
CD80 (B7-1) and CD86 (B7-2) are ligands of T cell critical costimulatory molecule CD28 and of an inhibitory receptor CTLA-4 ( ... CD80 is expressed by activated B cells, macrophages and dendritic cells. In addition, activated T cells express this antigen. ... Cell number should be determined empirically but can range from 10^5 to 10^8 cells/test. Super Bright 436 can be ... The interaction of CD28 and CD152 with CD80 is crucial in T-B cell communication leading to activation of T and B cells, ...
Costimulatory and inhibitory t-cell receptors/antagonists & inhibitors/metabolism (1). *Cyclooxygenase inhibitors/pharmacology ...
... costimulatory signal from one or more receptors. Engaging the costimulatory receptors on T cells to boost immunity is one new ... In contrast to PD-1 s inhibitory role in T cells, four other new targets play a costimulatory role, and researchers have ... GITR is another new costimulatory target. Like OX40, GITR is expressed after T-cell activation and enhances T-cell function and ... To trigger an adaptive immune response, an APC fi rst displays an antigen to T-cell receptors on neighboring T cells. After ...
  • CTLA-4 and PD-1) molecules (so-called immune checkpoints) on T cells play a crucial role in regulating T-cell activation to maintain the immune homeostasis in our bodies. (medscape.com)
  • Inhibitory receptors specific for MHC class I molecules with immunoreceptor tyrosine-based inhibitory motifs play a key role in preventing NK cell responses against normal autologous cells. (frontiersin.org)
  • This function is mainly fulfilled by members of the human killer-cell immunoglobulin-like receptor (KIR) family, which recognize sets of classical HLA class I (HLA-I) molecules, and by the CD94/NKG2A lectin-like heterodimer specific for HLA-E. Conversely, other KIRs and CD94/NKG2C, which display a lower affinity for HLA-I ligands trigger protein tyrosine kinase pathways through DAP12, an adaptor with immunoreceptor tyrosine-based activation motifs. (frontiersin.org)
  • With this remarkable exception, no formal proof has been thus far obtained supporting the involvement of other activating KIR, NKG2, or Ly49 receptors in direct recognition of pathogen molecules ( 6 ). (frontiersin.org)
  • Figure 3: Co-stimulatory and co-inhibitory molecules set thresholds for T-cell activation. (nature.com)
  • Receptor-ligand interaction is required for the transduction of second signal, following the first signal conveyed by the interaction of MHC molecules on APCs and T cell receptors on effector T cells loaded with cognate antigens [ 3 ]. (biomedcentral.com)
  • T cell activation is regulated by the innate immune system through positive and negative costimulatory molecules. (acrobiosystems.com.cn)
  • 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.nl)
  • To that end, several companies are developing drugs targeting molecules at the immunological synapse, the interface between T cells and antigen-presenting cells (APCs). (kengarber.com)
  • The two types of targets - costimulatory molecules and immune checkpoints - act in opposite ways. (kengarber.com)
  • Lay summary: Our research identified an important set of molecules, termed cytokines, that control how immune cells communicate with each other. (grantome.com)
  • We demonstrated that altering the activity of these molecules changes the responses of cells. (grantome.com)
  • CTLA4 is similar to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and B7-2, respectively, on antigen-presenting cells. (sciencellonline.com)
  • CTLA-4 is structurally similar to the T-cell co-stimulatory protein, CD28, and both molecules bind to the B7 family members B7-1 (CD80) and B7-2 (CD86). (bxcell.com)
  • A disturbed balance of costimulatory and inhibitory signals may result either in the failure of eliminating exogenous pathogens or in autoimmune diseases. (medscape.com)
  • The tumor microenvironment establishes complex networks to escape immune attacks where cytotoxic T-cell activity against tumors are perturbed by downregulated stimulatory signals, by upregulated inhibitory signals or by both. (medscape.com)
  • [ 81 ] The development of mAbs with either activating costimulatory signals (agonistic mAbs) or suppressing inhibitory signals (antagonistic mAbs) has induced the recovery of their cytotoxicity against exogenous pathogens and tumor cells. (medscape.com)
  • T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. (nih.gov)
  • A micrometer-scale receptor clustering integrated the TCR and CD28 signals required for IL-2 secretion in primary 5C.C7 T cells, a low-affinity/avidity TCR system. (elsevier.com)
  • Immune checkpoint proteins can regulate the immune response in malignancies and infectious diseases via numerous types of activating and inhibitory signals between antigen-presenting cells (APCs) and T cells [ 3 , 4 ]. (biomedcentral.com)
  • Based on the recognition of antigens in the adaptive immune response, T cell activity is largely achieved during activation, where two signals are required. (acrobiosystems.com.cn)
  • T cell activation and differentiation is dependent on TCR engagement of antigen and cooperating signals provided by several distinct receptor-ligand systems. (grantome.com)
  • The herpesvirus entry mediator (HVEM), a TNF superfamily member, engages LIGHT initiating costimulatory signals to T cells, yet HVEM also engages B and T lymphocyte attenuator (BTLA), an Ig superfamily member that provides an inhibitory signal to T cells. (grantome.com)
  • These plans will provide a mechanistic understanding of how LTap and LIGHT signals are integrated to orchestrate intercellular communication between T lymphocytes and dendritic cells during immune responses. (grantome.com)
  • PD-1's structure includes a ITIM (immunoreceptor tyrosine-based inhibitory motif) suggesting that PD-1 negatively regulates TCR signals. (bioxcell.com)
  • Hence, e.g., upon engulfment of bacterias, macrophages become antigen-presenting cells and offer costimulatory signals essential for complete lymphocyte activation (5). (icem2012.org)
  • T-cell activation and inactivation requires the coordination of various co-inhibitory and co-stimulatory signals which are modulated by most immunotherapeutic approaches. (tebu-bio.com)
  • Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. (unisr.it)
  • A largely overlooked immune cell type in the context of immunotherapies are B cells, which can exert both anti-tumour and tumour-promoting effects by providing co-stimulatory signals and inhibitory signals for T cell activation, cytokines, and antibodies. (labroots.com)
  • Co-stimulatory receptors consist of Compact disc28 and ICOS (inducible T cell co-stimulator) from the Ig superfamily, aswell as 4-1BB, OX40, Compact disc27, Compact disc30, Compact disc40, GITR (glucocorticoid inducible TNF receptor-related proteins), and HVEM (herpes-virus entrance mediator) from the TNFR superfamily [10, 11]. (cancer-ecosystem.com)
  • PD-1 is a 50-55 kDa cell surface receptor encoded by the Pdcd1 gene that belongs to the CD28 family of the Ig superfamily. (bioxcell.com)
  • CTLA4 is a member of the immunoglobulin superfamily, which is expressed on the surface of helper T cells and transmits an inhibitory signal to T cells. (sciencellonline.com)
  • PD-L2 is a 42 kDa type I transmembrane glycoprotein that belongs to the B7 family of the immunoglobulin (Ig) receptor superfamily. (leinco.com)
  • 4-1BB is also known as CD137, tumor necrosis factor receptor superfamily member 9 (TNFRSF9), induced by lymphocyte activation (ILA), is a co-stimulatory molecule of the tumor necrosis factor (TNF) receptor superfamily. (acrobiosystems.com)
  • [ 18 ] Clinical trials using T-cell checkpoint mAbs have also been performed in other types of cancer including CRC. (medscape.com)
  • Ongoing clinical trials of T-cell checkpoint mAbs in CRC include mAbs targeting CTLA-4, PD-1 and PD-L1. (medscape.com)
  • Antagonistic T-cell checkpoint mAbs, compared with mAbs with agonistic T-cell stimulating properties, are currently the primary focus of clinical trials, partly because an agonistic anti-CD28 mAb (TGN-1241) showed severe toxicity, such as multiorgan failures due to cytokine storm in a Phase I dose-escalation trial in 2006. (medscape.com)
  • Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, often exploited by many cancers. (discoverx.com)
  • Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca 2+ signaling and promote T cell survival. (mdpi.com)
  • Introduction Immune checkpoint inhibitors and adoptive T-cell therapy based on chimeric antigen receptors are the spearhead strategies to exploit the immune system to fight cancer. (unav.edu)
  • This provides a key checkpoint in the regulation of T cell immunity. (acrobiosystems.com.cn)
  • In addition, it requires suitable engagement of positive co-stimulatory substances on lymphocytes while restricting signaling through inhibitory immune system checkpoint receptors. (cancer-ecosystem.com)
  • TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains) is a novel negative immune checkpoint, expressed on T cells and NK cells. (genentechoncology.com)
  • CTLA-4 is among a group of inhibitory receptors being explored as cancer treatment targets through immune checkpoint blockade. (bxcell.com)
  • The team then showed that preventing PD-1 activation by blocking its ligands with antibodies restored T cell function and decreased viral load in the mice. (the-scientist.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.nl)
  • This paper examines available data on expression and regulation of immune co-modulatory (co-stimulatory and co-inhibitory) ligands on cancer stem cells in order to devise strategies to circumvent resistance. (imrpress.com)
  • Klinger M, Kim JK, Chmura SA , Barczak A, Erle DJ, Killeen N . Thymic OX40 expression discriminates cells undergoing strong responses to selection ligands. (academictree.org)
  • Bind to 8 different ligands that are expressed by a vast majority of cancer cells, both hemaetological and solid malignancies. (emjreviews.com)
  • Target and kill tumors as well as the blood vessels that feed them and also express the ligands of the NKG2D receptor. (emjreviews.com)
  • CTLA-4 (CD152), a homolog of the costimulatory molecule CD28, is a receptor for CD80 and CD86, and is essential for T-cell homeostasis and tolerance. (medscape.com)
  • The inhibitory receptor CTLA-4 is definitely a structural homolog of the costimulatory receptor Compact disc28 and stocks. (mindunwindart.com)
  • In particular, Toll-like receptors have been implicated in the development of B-cell autoimmunity, and genetic associations in Toll-receptor signalling pathways have been found in systemic lupus erythematosus. (nature.com)
  • Further investigations of PD-1 expression on exhausted T cells led to the discovery of a plethora of inhibitory pathways active during chronic infection. (the-scientist.com)
  • They noted that in HIV infection, CTLA-4 is selectively upregulated in CD4 T cells but not CD8 cells, demonstrating that different types of T cells utilize different combinations of inhibitory pathways. (the-scientist.com)
  • Here, blinatumomab-induced transcriptional changes reflected the functional immune activity of the blinatumomab-activated T cells, including the upregulation of pathways such as the immune system, glycolysis, IFNA signaling, gap junctions, and IFNG signaling. (biomedcentral.com)
  • There are a large number of costimulatory and coinhibitory pathways today. (mindunwindart.com)
  • Next, we shall review various other inhibitory pathways in the T7-Compact disc28 family. (mindunwindart.com)
  • Lee K, Gudapati P, Dragovic S , Spencer C , Joyce S , Killeen N , Magnuson MA , Boothby M. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. (academictree.org)
  • T lymphocytes are divided into two subsets by their expression of T cell antigen receptors (TCRs): αβ T cells (combination of an α chain and a β chain) and γδ T cells (combination of a γ chain and a δ chain). (springer.com)
  • Ipilimumab works by inhibiting one such molecule, CTLA4, a negative T-cell regulator, but other attractive targets also exist. (kengarber.com)
  • Recent insights into the interaction between professional antigen presenting cells, dendritic cells (DCs), and malaria parasites is discussed in detail. (jpgmonline.com)
  • The B and T lymphocyte attenuator is a type I transmembrane glycoprotein expressed at high levels on activated T cells and resting B cells and at lower levels on naive T cells, NK cells, bone marrow-derived dendritic cells, and splenic macrophages ( 1 , 2 ). (aai.org)
  • CD80 is expressed by activated B cells, macrophages and dendritic cells. (fishersci.nl)
  • Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). (isynbio.org)
  • Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. (isynbio.org)
  • 3R system, which together regulates the homeostasis and expansion of specific subsets of dendritic cells in lymphoid organs. (grantome.com)
  • HVEM-BTLA acts at a postmitotic step to limit dendritic cell expansion. (grantome.com)
  • The attenuation of death receptor signaling will be examined as one mechanism mediating the inhibitory affect of HVEM-BTLA on dendritic cell homeostasis using mouse and human models. (grantome.com)
  • CD80 is constitutively expressed on dendritic cells and monocytes/macrophages, and inducibly expressed on activated B and T cells. (biolegend.com)
  • The ligation of CD28 on T cells with CD80 and CD86 (B7-2) on antigen presenting cells (such as dendritic cells, macrophages, and B cells) elicits co-stimulation of T cells resulting in enhanced cell activation, proliferation, and cytokine production. (biolegend.com)
  • Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. (academictree.org)
  • PD-L2 is expressed on macrophages and a subset of dendritic cells (DCs). (leinco.com)
  • In addition, CD137 expression is found on dendritic cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation. (acrobiosystems.com)
  • Histiocytoses encompass a group of diverse proliferative disorders characterized by the accumulation and infiltration of variable numbers of monocytes, macrophages, and dendritic cells in the affected tissues. (medscape.com)
  • The virus is taken up by dendritic cells, which, after antigen processing, presents it to T cells, leading to immune activation and release of a cascade of cytokines that are believed to mediate the systemic effects of plasma leakage and circulatory insufficiency. (who.int)
  • In contrast to existing CAR-T cells, Celyad's lead immuno-oncology product candidate, NKR-2, is a T-Cell encoded to express the human Natural Killer activating receptor, NKG2D. (emjreviews.com)
  • Areas covered This review describes the basics of mRNA biotechnology and provides insight into the recent advances in the use of mRNA for the local and systemic delivery of immunostimulatory antibodies, proinflammatory cytokines or for optimizing adoptive T-cell therapy. (unav.edu)
  • Other biotechnology strategies such as IL-12-engineered local adoptive cell therapy and pro-cytokines can also be used to improve results and broaden the therapeutic window. (unav.edu)
  • This "priming" by the viral infection can change a 'cold' tumor microenvironment into a 'hot' one with the influx of a multitude of immune cells and cytokines. (springeropen.com)
  • Amongst others, proinflammatory cytokines and pathogen-associated molecular patterns induce activation from the IKK complicated by signaling via tumor necrosis aspect (TNF) receptor- or Toll-like receptor-interleukin-1 (IL-1) receptor superfamilies. (icem2012.org)
  • Cross-linking of IgE bound to mast cells by FcεRI triggers the release of preformed vasoactive mediators, synthesis of prostaglandins and leukotrienes, and the transcription of cytokines. (jci.org)
  • CTLA-4 is translocated onto the cell surface from the intracellular compartment upon T-cell activation and competes with CD28 for CD80 or CD86, or delivers an inhibitory signal directly through its cytoplasmic tail. (medscape.com)
  • PD-1 (CD279), also a homolog of CD28, is a receptor induced on the cell surface of activated T cells, B cells and myeloid cells. (medscape.com)
  • Co-stimulatory receptor-ligand interactions that help amplify effector T cell responses include CD28-CD80, 4-1BB (also known as CD137)-4-1BB ligand, CD27-CD70. (biomedcentral.com)
  • However, unlike typical T cell activation, blinatumomab-induced activation occurs independently of MHC I and additional T cell co-stimulatory factors, such as anti-CD28 antibody and interleukin-2. (biomedcentral.com)
  • CD80 has high affinity for binding to two T cell surface antigens, CD28 and CD152 (CTLA-4). (fishersci.nl)
  • 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.nl)
  • An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN . (nih.gov)
  • CTLA4 transmits an inhibitory signal to T cells, whereas CD28 transmits a stimulatory signal. (sciencellonline.com)
  • Foxp3 + -enriched Vδ2 + T cells, but not positively freshly isolated Vδ2 + T cells, displayed regulatory/immunosuppressive activity on αβ T cells when co-cultured with autologous PBMCs in the presence of anti-CD3/anti-CD28 mAb [ 21 ]. (springer.com)
  • 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. (bvsalud.org)
  • A highly effective immune system response requires enough numbers of turned on T cells with the capacity of spotting tumor antigens. (cancer-ecosystem.com)
  • Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. (harvard.edu)
  • In 2002, immunobiologist Leiping Chen, M.D., Ph.D., then at the Mayo Clinic in Rochester, Minn., reported that a variety of human tumors express PD-L1 (or B7-H1), the main ligand for PD-1, and that it increases apoptosis of tumor-specifi c T cells in vitro. (kengarber.com)
  • Introducing PD-L1 into tumors caused them to grow in mice, where T cells had previously kept them in check. (kengarber.com)
  • Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. (isynbio.org)
  • Induced PD-L1 expression is common in many tumors including squamous cell carcinoma, colon adenocarcinoma, and breast adenocarcinoma. (bioxcell.com)
  • TIGIT is a coinhibitory receptor that binds to PVR on APCs and tumor cells in various solid and hematologic tumors. (genentechoncology.com)
  • To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed E mu-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. (unisr.it)
  • It brings killer T and target B cells into close proximity, activating patient's autologous T cells to kill malignant B cells via mechanisms such as cytolytic immune synapse formation and inflammatory cytokine production. (biomedcentral.com)
  • Upon ligand binding, PD-1 signaling inhibits T-cell activation, leading to reduced proliferation, cytokine production, and T-cell death. (bioxcell.com)
  • Binding of PD-L2 to PD-1 on CD4 and CD8 T cells inhibits T cell receptor (TCR) signaling, negatively regulating T cell proliferation, cytokine production, and cytotoxic activity 2 . (leinco.com)
  • B cell are monoclonal, from one cancerous B cell expressing a distinctive immunoglobulin, as well as the adjustable region of the antibody (termed idiotype) continues to be utilized as a distinctive patient particular tumor antigen. (cancer-ecosystem.com)
  • TIGIT=T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains. (genentechoncology.com)
  • To accelerate biologics research and development, GenScript launched over 200 types of single clone-derived cell lines for cell-based bioassays that overexpressing trending targets, including Fc gamma receptors, neonatal Fc receptor, G protein-coupled receptors, co-inhibitory and co-stimulatory immune checkpoints, ACE2 and spike protein of SARS-Cov-2, and immunotherapeutic targets. (genscript.com)
  • Co-stimulatory (TNFRSF4 and TNFRSF18) and co-inhibitory (LAG3) receptors were similarly upregulated in blinatumomab-activated T cells, indicating ligand-dependent T cell functions. (biomedcentral.com)
  • Particularly, B-ALL cell expression of TNFSF4, which encodes the ligand of T cell co-stimulatory receptor TNFRSF4, was found positively correlated with the response to blinatumomab treatment. (biomedcentral.com)
  • My research focus is on understanding the characteristics and underlying mechanisms of co-inhibitory and co-stimulatory receptors on cancer-specific cytotoxic T cells and how this could be manipulated for future cancer immunotherapies. (ox.ac.uk)
  • secondly, co-stimulatory/ co-inhibitory receptors on T cells must bind B7 ligand family expressed on APCs to regulate situation of T cell. (acrobiosystems.com.cn)
  • Although Capital t cell costimulatory paths had been imagined as stimulators of Capital t cell reactions, it is certainly today very clear that there are both stimulatory (costimulatory) and inhibitory (coinhibitory) second indicators that modulate Testosterone levels cell receptor (TCR)-mediated Testosterone levels cell account activation. (mindunwindart.com)
  • Existing CAR-T cells are engineered using constructs encoding an antibody single chain variable fragment, the signaling domain of CD3 zeta and one or more co-stimulatory domain(s). (emjreviews.com)
  • Engagement of the receptor by solid-phase bound CD94- or NKG2C-specific monoclonal antibodies (mAbs) triggered Luc expression. (frontiersin.org)
  • Bi-specific T-cell engager (BiTE) antibody is a class of bispecific antibodies designed for cancer immunotherapy. (biomedcentral.com)
  • In mouse models of melanoma, tumor growth can be transiently arrested via treatment with antibodies which block the interaction between PD-L1 and its receptor PD-1. (bioxcell.com)
  • A few years later in 2014, the FDA approved nivolumab and pembrolizumab (both monoclonal antibodies targeting programmed death receptor 1 [PD-1]) for the treatment of advanced melanoma [ 6 ]. (springeropen.com)
  • Therefore a number of pharmaceutical companies are actively developing monoclonal antibodies targeting PD-1 and PD-L to boost the immune system for the treatment of non-small-cell lung cancer, melanoma, and bladder, renal, and triple-negative breast cancers. (tebu-bio.com)
  • For more than 20 years, scientists have trusted Bio X Cell as their go-to source for in vivo functional grade antibodies. (bxcell.com)
  • Functional grade preclinical antibodies are manufactured in an animal free facility using only In vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates. (leinco.com)
  • B-cells produce anti-tumour antibodies, which can potentially mediate antibody-dependent cellular cytotoxicity (ADCC). (labroots.com)
  • T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca 2+ ) concentration. (mdpi.com)
  • [10] During this time, cytotoxic T cells (CTLs) and IFN gamma-producing cells can promote elimination of intracellular parasites. (jpgmonline.com)
  • For optimal T-cell activation, T-cell receptor ligation to peptide-MHC complexes combined with costimulatory (i.e. (medscape.com)
  • Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. (nih.gov)
  • Co-receptors stabilize interactions between the TCR and its ligand, the peptide-major histocompatibility complex (pMHC), and enhance Ca 2+ signaling and T cell activation. (mdpi.com)
  • Conversely, some co-receptors can dampen Ca 2+ signaling and inhibit T cell activation. (mdpi.com)
  • A family of receptors that modulate the activation of T-LYMPHOCYTES by the T-CELL ANTIGEN RECEPTOR. (bvsalud.org)
  • During T cell activation, T cell receptors (TCR) cluster at the center of the T cell/antigen-presenting cell interface forming a key component of the immunological synapse. (elsevier.com)
  • Figure 6: Activation of interferon production through TLR7 and TLR9 receptors. (nature.com)
  • How PD-1 blocks T cell activation is still an open question, says Ahmed. (the-scientist.com)
  • In this study, we performed single-cell sequencing analysis to identify transcriptional changes in T cells following blinatumomab-induced T cell activation using single cells from both, a human cell line model and a patient-derived model of blinatumomab-mediated cytotoxicity. (biomedcentral.com)
  • These results reveal a target cell-dependent mechanism of T-cell activation by blinatumomab and suggest that TNFSF4 may be responsible for the resistant mechanism and a potential target for combination therapy with blinatumomab, to treat B-ALL or other B-cell malignancies. (biomedcentral.com)
  • The B and T lymphocyte attenuator (BTLA) appears to act as a negative regulator of T cell activation and growth. (aai.org)
  • SU-5402 Activation from the anti-tumor response through vaccination Applying concepts of vaccination towards the advancement of cancers vaccines has established challenging, most likely because cancers cells possess arisen from regular self tissues , nor trigger activation from the disease fighting capability as SU-5402 would microbial microorganisms. (cancer-ecosystem.com)
  • Promoting T cell function by modulating co-stimulation or co-inhibition Defense activation is firmly governed by co-receptors portrayed on T cells (Amount 1). (cancer-ecosystem.com)
  • Furthermore, although Testosterone levels cell costimulation was envisaged to control preliminary account activation of unsuspecting Testosterone levels cells, Testosterone levels cell costimulatory and coinhibitory paths have got very much broader immunoregulatory features, managing effector, storage and regulatory Rabbit polyclonal to AK3L1 Testosterone levels cells, as well as unsuspecting Testosterone levels cells. (mindunwindart.com)
  • These paths are crucial government bodies of Testosterone levels cell account activation, patience, and Testosterone levels cell tiredness, and healing modulation of costimulatory and coinhibitory paths is certainly converting to effective brand-new strategies for dealing with cancers, autoimmune and contagious illnesses, and transplant being rejected. (mindunwindart.com)
  • Oddly enough, accelerated eradication of in NF-B-inhibited macrophages is normally connected with decreased antigen-specific T-cell activation in macrophage-lymphocyte cocultures. (icem2012.org)
  • These data claim that inhibits PICD of macrophages via traditional, antiapoptotic NF-B activation and facilitates signaling to T cells thus. (icem2012.org)
  • Marques R, Williams A, Eksmond U, Wullaert A, Killeen N , Pasparakis M, Kioussis D, Kassiotis G. Generalized immune activation as a direct result of activated CD4+ T cell killing. (academictree.org)
  • Blockade of PD-L1 enables the activation of T-cells, restoring their ability to detect and attack tumor cells. (tebu-bio.com)
  • Evidence in humans and animal models suggests that IgE-mediated mast cell activation gives rise to both the acute and late-phase responses. (jci.org)
  • Acute responses are accompanied by evidence of mast cell activation and mediator release. (jci.org)
  • In conclusion, pharmacologic stimulation of Vδ2 + T cells via the Vδ2 TCR for activation and expansion induces Vδ2 + T cells' potent killer activity while simultaneously licensing them to suppress αβ T cell responses. (springer.com)
  • an in vitro study suggested that tumor-infiltrating γδ T cells inhibit αβ T cell activation via PD-1/PD-L1 ligation [ 19 ]. (springer.com)
  • Its receptor, PD-1, is expressed by CD4-CD8- thymocytes as well as CD4 and CD8 T cells, monocytes, DCs, and B cells upon activation 1 . (leinco.com)
  • CD137 can enhance activation-induced T cell apoptosis when triggered by engagement of the TCR/CD3 complex. (acrobiosystems.com)
  • CD80 can also bind to CD152, also known as CTLA-4, to deliver an inhibitory signal to T cells. (biolegend.com)
  • CTLA4 (Cytotoxic T-Lymphocyte Antigen 4), also known as CD152 (cluster of differentiation 152), is a receptor protein that down-regulates the immune system. (sciencellonline.com)
  • The mechanisms underlying the development of adaptive NK cells remain uncertain but some observations support the involvement of a cognate interaction of CD94/NKG2C with ligand(s) displayed by HCMV-infected cells. (frontiersin.org)
  • In general, T-cell tolerance is effected 'centrally' in the thymus, or peripherally through the action of regulatory T cells or other mechanisms. (nature.com)
  • Structural mechanisms determining inhibition of the collagen receptor DDR1 by selective and multi-targeted type II kinase inhibitors. (harvard.edu)
  • However, the activated T-cell subtypes and the target cell-dependent T cell responses induced by blinatumomab, as well as the mechanisms of resistance to blinatumomab therapy are largely unknown. (biomedcentral.com)
  • With an improved understanding of how tumor cells evade anti-tumor response, there has been considerable effort to exploit these mechanisms for therapeutic targeting. (jcancer.org)
  • We found that LIGHT in either its membrane or soluble position modifies the binding of HVEM to BTLA, thus the mechanisms controlling the cellular compartmentalization of LIGHT may influence inhibitory signaling by BTLA. (grantome.com)
  • Target and kill the inhibitory mechanisms preventing the tumor from evading the immune system. (emjreviews.com)
  • Later, once the T cell is activated against a foreign antigen, one or more negative regulators, or immune checkpoints, come into play, dampening the immune response. (kengarber.com)
  • [ 83 ] In addition to effector T cells, CTLA-4 on Tregs also play an important role for the maintenance of T-cell homeostasis. (medscape.com)
  • It is also known as an 'exhaustion' marker of effector T cells under tumor-bearing conditions [ 17 ] and PD-1 expression is inversely associated with impaired cytokine secretion such as IFN-γ, TNF-α and IL-2 of tumor antigen-specific CD8 + T cells. (medscape.com)
  • Innate immune system cells, such as for example macrophages, are crucial for the web host to regulate and remove invading pathogens efficiently. (icem2012.org)
  • We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. (isynbio.org)
  • Despite recent progress in the understanding of γδ T cells' roles and functions, their interaction with αβ T cells still remains to be elucidated. (springer.com)
  • ACROBiosystems has developed exclusive B7 family proteins with high purity and high bioactivity, which are suitable for immune, antibody screening, SPR, cell activity detection and other experiments, and can accelerate the development of antibody drugs. (acrobiosystems.com.cn)
  • PD-1 is transiently expressed on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. (bioxcell.com)
  • Additionally, Pdcd1 mRNA is expressed in developing B lymphocytes during the pro-B-cell stage. (bioxcell.com)
  • Cancer stem cells resistance to treatments may relate to inherent insensitivity to external apoptotic stimuli and, thus, may extend to immune therapies by inhibiting the actions of Cytotoxic T Lymphocytes (CTLs) in the tumor micro-environment. (imrpress.com)
  • In their recent study (1) and film (2), the research team captured real-time behaviour of Cytotoxic T lymphocytes (CTLs) hunting down, moving and killing cancer cells. (tebu-bio.com)
  • To determine the effects of PD-1 pathway blockade on sarcoidosis CD4 + T-cell proliferative capacity. (atsjournals.org)
  • Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage-derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. (atsjournals.org)
  • Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4 + T-cell proliferative capacity and clinical outcome. (atsjournals.org)
  • In 2006, however, Rafi Ahmed, of the Emory University School of Medicine, and colleagues discovered that the PD-1 pathway could also be exploited by pathogens to repress normal T cell function during chronic viral infection. (the-scientist.com)
  • In 30 to 40 subsequent papers, says Ahmed, upregulated expression of the PD-1 pathway has been firmly documented as a mechanism of T cell dysfunction in the three main human chronic viral infections - HIV, hepatitis B, and hepatitis C - as well as SIV infection in non-human primates. (the-scientist.com)
  • Around the same time, researchers identified a second reversible pathway involved in HIV T cell inhibition. (the-scientist.com)
  • Based on evolutionary considerations, the initial function 7-Amino-4-methylcoumarin from the NF-B pathway may be the initiation of irritation and innate immune system responses via creation of inflammatory mediators and recruitment of immune system cells (17, 39). (icem2012.org)
  • A unique and specific feature of human Vγ9Vδ2 T cells (Vδ2 + T cells) is their TCR-dependent recognition of phosphoantigens (PAgs), metabolites of the phosphorylated isoprenoid pathway. (springer.com)
  • When co-cultured with Human 4-1BB (Luc) HEK293 Reporter Cell and anti-4-1BB agonist antibody, the anti-4-1BB antibody can be crosslinked, thereby strengthening 4-1BB pathway-activated luminescence. (acrobiosystems.com)
  • Human cytomegalovirus (HCMV) infection promotes the differentiation and persistent expansion of a mature NK cell subset, which displays high surface levels of the activating CD94/NKG2C NK cell receptor, together with additional distinctive phenotypic and functional features. (frontiersin.org)
  • The results are discussed in the framework of previous observations supporting the hypothetical existence of specific ligand(s) for CD94/NKG2C in HCMV-infected cells. (frontiersin.org)
  • In this regard, human cytomegalovirus (HCMV) infection has been shown to promote the differentiation and persistent expansion of a mature NK cell subset, which displays high surface levels of the activating CD94/NKG2C NKR (NKG2C bright ), together with additional distinctive phenotypic and functional features ( 7 - 12 ). (frontiersin.org)
  • 1. Distribution of HLA-E and its inhibitory receptors CD94/NKG2a and exploitation of this machinery by cancer to inhibit anti-tumor T cell responses. (ox.ac.uk)
  • Similar inhibitory and activating NK cell receptors (NKR) have been identified among the murine Ly49 and NKG2 lectin-like receptor families ( 1 , 2 ). (frontiersin.org)
  • 3 Microarray data not only revealed "striking" levels of PD-1 expression on the chronically infected T cells, says Wherry, but expression of a whole set of inhibitory genes, including those for known inhibitory receptors like 2B4, Ly49 family members, and GP49B. (the-scientist.com)
  • 3. Epigenetic regulation of effector cytokine responses of cancer-specific T cells. (ox.ac.uk)
  • Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses. (ox.ac.uk)
  • Members of the B7 family have been shown to be important for regulating T cell responses. (acrobiosystems.com.cn)
  • T cell homeostasis and inflammatory responses. (grantome.com)
  • Th2 cells are critical in maintaining both the state of chronic and relapsing eosinophil-predominant inflammation and the acute hypersensitivity responses characteristic of the atopic diseases. (jci.org)
  • IgE functions in allergic responses: immediate hypersensitivity, allergen focusing, and IgE receptor regulation. (jci.org)
  • IgE-induced mast cell degranulation in vivo is often followed by a late-phase reaction (LPR), a second wave of hypersensitivity responses occurring many hours after the acute reaction and dependent upon eosinophils. (jci.org)
  • Upon ligand binding, CTLA-4 negatively regulates cell-mediated immune responses. (bxcell.com)
  • Gicobi JK, Dellacecca ER, Dong H . Resilient T-cell responses in patients with advanced cancers. (mayo.edu)
  • We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. (unisr.it)
  • In March 2016, Mark J Osborn et al published in Molecular Therapy a major article for genome editing (doi:10.1038/mt.2015.197), about knock-out of CD3 in human T-cells. (tebu-bio.com)
  • Binding of PD-L1 to PD-1 negatively regulates T cell signaling and inhibits cytotoxic T-cell activity. (tebu-bio.com)
  • We found that negatively freshly isolated Vδ2 + T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). (springer.com)
  • 4 In the study, Daniel Kaufmann, an instructor at PARC, and colleagues showed that blocking CTLA-4, another inhibitory immunoregulatory receptor, can also reverse T cell dysfunction in chronic infection. (the-scientist.com)
  • Engaging the costimulatory receptors on T cells to boost immunity is one new anticancer treatment strategy. (kengarber.com)
  • Pre-clinical and clinical data have shown that oncolytic vectors can induce anti-tumor immunity and markedly increase immune cell infiltration (including cytotoxic CD8 + T cells) into the local tumor microenvironment. (springeropen.com)
  • Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. (atsjournals.org)
  • Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. (atsjournals.org)
  • Enhanced inhibitory receptor expression has been reported in lung cancers, but its role in idiopathic lung disease, such as sarcoidosis, is unknown. (atsjournals.org)
  • While the percentages of CD56 (dim) cells and their CD16 expression were lower in the chronic group, this was not statistically significant. (who.int)
  • Last year, Ahmed and Wherry examined the molecular signature of T cell exhaustion by comparing gene expression profiles of infected and functional CD8 T cells in mice. (the-scientist.com)
  • The panels on the right show the expression of curated gene sets in the cell types defined in the left panel. (isynbio.org)
  • Background: Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. (jcancer.org)
  • Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response. (jcancer.org)
  • Patients and Methods: A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative immunofluorescence. (jcancer.org)
  • Blockade of CTLA4 expression in vitro augments HIV-specific CD4-positive T-cell function. (sciencellonline.com)
  • This therapeutic appraoch is based on the observation that PD-1 expression is upregulated by virus-specific T cells and that the inhibition of this loop is hoped to decrease viral load by increasing T cell function. (tebu-bio.com)
  • Vδ2 + T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. (springer.com)
  • The Cell-based Kit consists of two engineered cell lines, Human 4-1BB (Luc) HEK293 Reporter Cell (Cat.No.CHEK-ATF073) and CHO/Human CD32a Stable Cell Line (Low Expression) (Cat.No.SCCHO-ATP061L). (acrobiosystems.com)
  • The CHO/Human CD32a Stable Cell Line was engineered to express full length human CD32a receptor (Gene ID: 2212), with different levels of CD32a expression (High, Medium, Low), which can be used to test agonist antibody whether in a CD32a-dependent manner to strengthen the agonistic activity. (acrobiosystems.com)
  • Expression analysis of human 4-1BB on Human 4-1BB (Luc) HEK293 Reporter Cell by FACS. (acrobiosystems.com)
  • Expression analysis of human CD32a on CHO/Human CD32a Stable Cell Line by FACS. (acrobiosystems.com)
  • [ 84 ] Antitumor efficacy of antagonistic anti-CTLA-4 mAb was demonstrated in a murine colon tumor model [ 85 ] and CTLA-4 signaling blockade improved T-cell proliferation, Th1 cytokine secretion and decreased the threshold of tumor-associated antigen recognition. (medscape.com)
  • Central TCR accumulation thus had a specific role in signaling integration in low-affinity T cells. (elsevier.com)
  • The tail then binds phosphatases in the T cell, triggering a downregulation of antigen receptor signaling. (the-scientist.com)
  • During traditional NF-B signaling, turned on IKK catalyzes the phosphorylation of inhibitory IBs, which is normally accompanied by their polyubiquitination and proteasomal degradation. (icem2012.org)
  • The Human 4-1BB (Luc) HEK293 Reporter Cell was engineered to not only express NF-κB signaling response element, but also express the receptor full length human 4-1BB (Gene ID: 3604), which can drive luciferase expressing systems by 4-1BB ligand/ agonist antibody stimulation. (acrobiosystems.com)
  • In addition, parasite interactions with the different effector arms of the immune system can result in altered peptide ligand (APL) antagonism which alters the immune response from a pro- to an anti-inflammatory T cell response. (jpgmonline.com)
  • It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. (nih.gov)
  • With the discovery of VHL alterations in the majority of clear cell RCCs, targeted therapies were studied in this population. (jcancer.org)
  • In addition, the Company is developing a next generation portfolio of CAR T-cell therapies that utilize human Natural Killer cell receptors for the treatment of numerous blood and solid cancers. (emjreviews.com)
  • Receptors, Mitogen" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • This graph shows the total number of publications written about "Receptors, Mitogen" by people in Harvard Catalyst Profiles by year, and whether "Receptors, Mitogen" was a major or minor topic of these publication. (harvard.edu)
  • Below are the most recent publications written about "Receptors, Mitogen" by people in Profiles. (harvard.edu)
  • ABSTRACT Natural killer (NK) cells are key players in the immune response to viruses. (who.int)
  • Freeman agrees, and notes that because PD-L1 binds two inhibitory receptors, it may play a more crucial role in immune response than previously believed. (the-scientist.com)
  • there are still conflicts in results about their respective roles in initiation or sustaining of the T cell immune response. (fishersci.nl)
  • To trigger an adaptive immune response, an APC fi rst displays an antigen to T-cell receptors on neighboring T cells. (kengarber.com)
  • 1-3 TIGIT dampens the immune response by competing with its costimulatory counterpart, CD226, for binding to PVR. (genentechoncology.com)
  • As the millennium draws to a close, it is clear that IgE production represents only one feature of a larger specific immune response orchestrated by the Th2 subset of CD4 + Th cells. (jci.org)
  • Induces adaptive auto-immune response thanks to the creation of a long term cell memory against the targeted tumor. (emjreviews.com)
  • Recent advances in single-cell RNA sequencing (scRNA-seq) are opening a new way for evaluating transcriptional features with cellular resolution in various types of cancers.11,12,13,14 This study represents a comprehensive and unique resource revealing the cellular heterogeneity of NPC TME at single-cell resolution. (isynbio.org)
  • A randomized trial of 512 metastatic prostate cancers sufferers reported a 4.four weeks upsurge in median survival in individuals receiving Sipuleucel-T, a vaccine comprising autologous peripheral blood mononuclear cells pulsed using a fusion protein of GM-CSF as well as the prostate cancer antigen prostatic acid phosphatase [3]. (cancer-ecosystem.com)
  • 5 B7-1 binds the PD-1 ligand, PD-L1, as well and also induces an inhibitory signal in T cells. (the-scientist.com)
  • Immobilized cell surface PD-1 (5x104 of cells per well) can bind Human PD-L1, Fc Tag (Cat. (acrobiosystems.com.cn)
  • Cell surface receptors containing an immunoglobin domain. (embl.de)
  • PD-1 is a receptor present on the surface of activated T-cells and other immune cells. (tebu-bio.com)
  • Cell surface staining was performed on Human 4-1BB (Luc) HEK293 Reporter Cell or negative control cell using PE-labeled anti-human 4-1BB antibody. (acrobiosystems.com)
  • Similarly, engagement of PD-1 by PD-L2 dramatically inhibits T-cell proliferation, especially in CD4+ (T helper) cells. (tebu-bio.com)
  • Fine tuning of TLR and IL-1R-like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. (unisr.it)
  • Other genes are common and have more subtle 'threshold' effects on T-cell reactivity. (nature.com)
  • Although commonly referred to as costimulatory receptors, some of the receptors have inhibitory effects such as inducing PERIPHERAL TOLERANCE . (bvsalud.org)