Receptors, Antigen, T-Cell: 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.Receptors, Antigen, T-Cell, alpha-beta: 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.T-Lymphocytes: 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.Lymphocyte Activation: 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.Antigens, CD80: 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.Antigens, CD28: 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.CD4-Positive T-Lymphocytes: 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.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Antigens, CD: 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.Receptors, Antigen, T-Cell, gamma-delta: 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).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).Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Antigens, CD86: 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.Thymus Gland: 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.Mice, Inbred C57BLCD8-Positive T-Lymphocytes: 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, Differentiation, T-Lymphocyte: 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.Flow Cytometry: 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.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Mice, Inbred BALB CClone Cells: 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)Signal Transduction: 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.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Receptor-CD3 Complex, Antigen, T-Cell: 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.Dendritic Cells: 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).Genes, T-Cell Receptor beta: 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.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.Molecular Sequence Data: 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.Immunologic Memory: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.CTLA-4 Antigen: 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.Interferon-gamma: 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.Mice, Knockout: 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.Immunoconjugates: 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.B-Lymphocytes: 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.Antigens, CD4: 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.Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.Cytokines: 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, Differentiation: 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.Amino Acid Sequence: 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.T-Lymphocytes, Regulatory: 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.Complementarity Determining Regions: 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).Antigens, CD8: 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.Major Histocompatibility Complex: 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.Histocompatibility Antigens Class II: 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, Monoclonal: Antibodies produced by a single clone of cells.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Antigen-Presenting Cells: 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.Genes, T-Cell Receptor alpha: 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.Inducible T-Cell Co-Stimulator Protein: 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.CD40 Ligand: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.T-Lymphocytes, Cytotoxic: 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.Genes, T-Cell Receptor: 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.Immune Tolerance: 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.Models, Immunological: 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.Pre-B Cell Receptors: 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, Cultured: 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.Adoptive Transfer: 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).Epitopes, T-Lymphocyte: 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.Ligands: 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)Antigens, CD40: 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.Receptors, Antigen, B-Cell: 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.Hybridomas: 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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Cytotoxicity, Immunologic: 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.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): 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.Antigens, CD45: 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.Clonal Anergy: 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.Th1 Cells: 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.Killer Cells, Natural: 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.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Peptides: 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.Th2 Cells: 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, Interleukin-2: 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.Gene Rearrangement, delta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors.H-2 Antigens: The major group of transplantation antigens in the mouse.Antigen Presentation: 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)Lectins, C-Type: 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, Surface: 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.T-Lymphocytes, Helper-Inducer: 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.Inducible T-Cell Co-Stimulator Ligand: 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.Interleukin-4: 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.Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.4-1BB Ligand: 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.Receptors, Immunologic: 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.Antigens, CD137: 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.Lymphocyte Count: The number of LYMPHOCYTES per unit volume of BLOOD.Isoantigens: 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.Superantigens: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Histocompatibility Antigens Class I: 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.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Receptors, OX40: 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.Mice, Inbred Strains: 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.Epitopes: Sites on an antigen that interact with specific antibodies.Antigens, CD58: 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.Antigens, CD2: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Coculture 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.Antigens, CD274: 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.Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Immunophenotyping: 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.Gene Expression Regulation: 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.B7 Antigens: 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.Antigens, CD27: 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.Histocompatibility Antigens: 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.Protein Binding: 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.Immunological Synapses: 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.NFATC Transcription Factors: 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, Natural Killer Cell: 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.Genes, T-Cell Receptor delta: DNA sequences encoding the delta chain of the T-cell receptor. The delta-chain locus is located entirely within the alpha-chain locus.Down-Regulation: 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.HLA-DR Antigens: 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.Mice, Inbred DBACell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell SeparationInterleukin-12: 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.Up-Regulation: 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.HLA-A2 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.Immunotherapy, Adoptive: 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)Membrane Proteins: 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.Self Tolerance: 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.Adjuvants, Immunologic: 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.Myelin Basic Protein: 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.Clonal Deletion: 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.Adaptor Proteins, Signal Transducing: 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 enzymesMice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Immunity, Cellular: 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, RAG-1: 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.Cell Communication: 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.Lymphocyte Culture Test, Mixed: 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.Interleukin-2 Receptor alpha Subunit: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Interleukin-10: 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, Blocking: 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)Encephalomyelitis, Autoimmune, Experimental: 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)Minor Lymphocyte Stimulatory Antigens: 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).Mice, Inbred C3HTransfection: 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.Immunoglobulin Variable Region: 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.T-Cell Antigen Receptor Specificity: 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.Antigens, Neoplasm: 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.Immunoglobulins: 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 Fusion Proteins: 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, Messenger: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Polymerase Chain Reaction: 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.Lymphocyte Depletion: 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.Mice, Inbred CBALymphocyte Cooperation: T-cell enhancement of the B-cell response to thymic-dependent antigens.Mice, Inbred NOD: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Muromonab-CD3: Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).Antigens, CD1d: A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.Apoptosis: 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.Genes, T-Cell Receptor gamma: 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.Lymphopenia: Reduction in the number of lymphocytes.Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.Lymphocyte Function-Associated Antigen-1: 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.Programmed Cell Death 1 Ligand 2 Protein: 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.Antigens, CD70: 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.Antigens, CD1: 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.Costimulatory and Inhibitory T-Cell Receptors: 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.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Antigens, CD5: 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-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Reverse Transcriptase Polymerase Chain Reaction: 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.Mice, Inbred AKREnterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.Interleukin-15: 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.Tumor Cells, Cultured: 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.Programmed Cell Death 1 Receptor: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Immunization: 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).Cancer Vaccines: 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.NK Cell Lectin-Like Receptor Subfamily B: A subclass of NK cell lectin-like receptors that includes both inhibitory and stimulatory members.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Cytotoxicity Tests, Immunologic: The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.OX40 Ligand: 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.Intercellular Adhesion Molecule-1: 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.Antigens, Ly: A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.Mice, SCID: 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.Perforin: 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.Lymphoid Tissue: 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.DNA-Binding Proteins: 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.Natural Killer T-Cells: 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.Tumor Necrosis Factors: 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, Tumor-Infiltrating: 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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Antigens, CD95: 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.DNA Primers: 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.Immunosuppressive Agents: 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.Interleukin-17: 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.

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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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 ...
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.. ...
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
Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. SIGLECs are typically ... 2002). "Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone". Nat. Cell Biol. 4 ... It is also reported to bind to Vascular adhesion protein 1 (VAP-1) and to the co-stimulatory molecule CD24 also known as HSA ( ... expressed on cells of the innate immune system, with the exception of the B-cell expressed SIGLEC6 (MIM 604405).[supplied by ...
Cell to cell contact: Type 1 regulatory T cells poses inhibitory receptor CTLA-4 through which they exert suppressor function. ... IL-10 indirectly downregulates MHC II molecules and co-stimulatory molecules on antigen-presenting cells (APC) and force them ... Tr 1 cells) are a class of regulatory T cells participating in peripheral immunity as a subsets of CD4+ T cells . Tr1 cells ... The suppressing and tolerance-inducing effect of Tr1 cells is mediated mainly by cytokines. The other mechanism as cell to cell ...
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 ...
KIR - short for Killer-cell Immunoglobulin-like Receptor, is a receptor for MHC Class I molecules on Natural Killer cells. ... B7-H3 - also called CD276, was originally understood to be a co-stimulatory molecule but is now regarded as co-inhibitory. The ... Its ligand is ICOSL, expressed mainly on B cells and dendritic cells. The molecule seems to be important in T cell effector ... CD137-mediated signaling is also known to protect T cells, and in particular, CD8+ T cells from activation-induced cell death. ...
Fc receptors are found on many immune system cells, including natural killer cells. When natural killer cells encounter ... 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 ... In normal physiology T-cells are activated by two signals: the T-cell receptor binding to an antigen-MHC complex and T-cell ...
Coggeshall KM (June 1998). "Inhibitory signaling by B cell Fc gamma RIIb". Current Opinion in Immunology. 10 (3): 306-12. doi: ... a key subset for the generation of autoantibody producing autoreactive plasma B cells.[59] A balance among costimulatory and ... On NK cellsEdit. The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and ... Langerhans cells Phagocytosis. Degranulation (eosinophils) FcγRIIB1 (CD32) IgG Low (Kd , 10−7 M) B Cells. Mast cells No ...
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 the early 1990s, Jim Allison and Jeff Bluestone showed that CTLA-4 acts as an inhibitory molecule to restrict T cell ... This concept of blocking T-cell inhibitory pathways as a way of unleashing anti-tumor immune responses and eliciting clinical ...
CTLA4 is also found in regulatory T cells and contributes to its inhibitory function. T cell activation through the T cell ... CTLA4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and ... Biochemical evidence suggested that CTLA-4 recruits a phosphatase to the T cell receptor (TCR), thus attenuating the signal. ... and have low CTLA4 protein expression in T regulatory cells, hyperactivation of effector T cells, low switched memory B cells, ...
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 ...
In the resting T-cell there is no net phosphorylation of CD28 (one of the molecules providing co-stimulatory signals required ... However, when these antibodies are immobilized (either by secondary antibody bound to plastic or by Fc receptors on other cells ... size-based exclusion of inhibitory molecules from the contact site is not the only segregation model suggested for T-cell ... T-cell activation does not proceed. The TCR/peptide-MHC complex, formed when a T-cell recognizes its ligand and the T-cell-APC ...
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 ...
... binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition ... The binding of PD-L1 to PD-1 or B7.1 transmits an inhibitory signal that reduces the proliferation of these T cells and can ... "Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target". ... PD-L1 is expressed on T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells. ...
"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 ...
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 encodes the ... 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 ...
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 ...
... 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"), ...
The mAb causes the release of HIV-1-inhibitory b-chemokines, preventing other cells from becoming infected. Cancer-based ... Analysis of the CD4 coreceptor and activation-induced costimulatory molecules in antigen-mediated mature T lymphocyte death. ... 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 ...
NK cells), B cells and dendritic cells, being a ligand for MHC class II molecules. On T cells LAG-3 is an inhibitory receptor. ... an up-regulation of co-stimulatory molecules, and the production of IL-12 and TNF-α. A February 2003 paper in the journal ... IMP321 is manufactured in CHO cells. Immutep worked with Lonza in 2012 on cell line selection, master cell banking and process ... LAG3 is expressed on various cells in the immune system including activated T cells, Natural Killer cells ( ...
"PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells". EMBO Molecular Medicine. 3 ... Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. One ligand-receptor interaction under ... "Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses". Immunity ... PD-L1 on the cell surface binds to PD1 on an immune cell surface, which inhibits immune cell activity. Among PD-L1 functions is ...
T cell are less dependent on costimulatory signals and higher antigen concentration than naive T cell. The signal from the T- ... CD45 dephosphorylates inhibitory tyrosine of membrane-localized Src family kinases Fyn and Lck, previously recruited and ... On helper T cells and regulatory T cells, this co-receptor is CD4 that is specific for MHC class II. On cytotoxic T cells, this ... T cells expressing this receptor are referred to as α:β (or αβ) T cells, though a minority of T cells express an alternate ...
... a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells". Journal of ... "Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated ... Growth hormone receptor, HoxA10, Insulin receptor, Insulin-like growth factor 1 receptor, IRS1, Janus kinase 1, Janus kinase 2 ... Feng GS (2007). "Shp2-mediated molecular signaling in control of embryonic stem cell self-renewal and differentiation". Cell ...
"Entrez Gene: TREML1 triggering receptor expressed on myeloid cells-like 1". Strausberg RL, Feingold EA, Grouse LH, et al. (2003 ... a putative inhibitory receptor within the TREM cluster". Blood. 100 (10): 3822-4. doi:10.1182/blood-2002-02-0523. PMID 12393607 ... a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than ... 2006). "The structure of the extracellular domain of triggering receptor expressed on myeloid cells like transcript-1 and ...
... which has co-stimulatory role in B and T cells. CD200 (OX-2) is a type 1 membrane glycoprotein, which delivers an inhibitory ... The cell surface receptor interleukin-3 receptor-alpha (CD123) is overexpressed on CD34+CD38- leukemic stem cells (LSCs) in ... IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells". Cell Stem Cell. 5 (1): 31-42. doi:10.1016/j. ... "Critical appraisal of the side population assay in stem cell and cancer stem cell research". Cell stem cell. 8 (2): 136-47. doi ...
... by killer inhibitory and killer activatory receptor on NK cells and by various receptors on other cells including Fc receptor ... affinity T cell down-modulation of costimulatory molecules on dendritic cells mediated by T cells leads to regulation of T cell ... On T cells and B cells, trogocytosis is triggered when the T cell receptor (TCR) on T cells or B cell receptor (BCR) on B cells ... Epratuzumab (a CD22 Mab) acts using trogocytosis to transfer CD22 and other B-cell proteins from B cells to effector cells. ...
When a T-cell receptor is activated by contact with a peptide:MHC complex, CD45 dephosphorylates inhibitory tyrosine of ... T cell are less dependent on costimulatory signals and higher antigen concentration than naive T cell.[16] ... T cells expressing this receptor are referred to as α:β (or αβ) T cells, though a minority of T cells express an alternate ... The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes,[1] that is responsible for ...
... and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and costimulatory receptors. ... and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and costimulatory receptors. ... NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors ... NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors ...
Better Cell-Based Assays to Measure Co-Inhibitory and Co-Stimulatory Receptors in the Development of Therapeutic Antibodies. ... Cell Biology Cell Health Cell Line + Sample Identification Cell Signaling Energy Metabolism Imaging + Immunological Detection ... Co-stimulatory receptors: GITR, CD40, OX40, 4-1BB. Current approaches to measure the potency of immunotherapy drugs include in ... Somberg worked at Life Technologies where he led product development and service efforts in biochemical and cell-based assays ...
Conditioning of antigen-specific T-cells by activated and antigen-pulsed MSCs prevented T-cells to proliferate upon subsequent ... Conditioning of antigen-specific T-cells by activated and antigen-pulsed MSCs prevented T-cells to proliferate upon subsequent ... In sum, activation of MSCs with inflammatory stimuli turns these cells into suppressive cells, capable of mediating adaptive ... In sum, activation of MSCs with inflammatory stimuli turns these cells into suppressive cells, capable of med... ...
... cell-based reporter bioassays for the development of therapeutic antibodies targeting co-inhibitory immune checkpoint receptors ... and co-stimulatory (e.g. GITR, 4-1BB, OX40, CD40) receptors. Here we describe the application of cell-based reporter bioassays ... Activation of T cells via direct stimulation of the T cell receptor or by modulating immune checkpoint pathways are two ... Quantitative Cell-Based Bioassays for Individual or Combination Immune Checkpoint Immunotherapy. Part # PS290 ...
Negative feedback of T cell activation through inhibitory adapters and costimulatory receptors. Immunol. Rev. 192:143. ... converts CTLA-4 from an inhibitory receptor into an activating receptor for T cells. Because the T cell response to 24:26 ... Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J. Exp. Med. 160:1284. ... by which a bispecific tandem ScFv ligand of CTLA-4 converts this inhibitory receptor on T cells into an activating receptor. ...
Immune cell function implicates important modulators known as cosignaling receptors. On T cells, the cosignaling receptors ... The CD28 immunoglobulin-superfamily is composed of coinhibitory and costimulatory receptors. Programmed Death-1 (PD-1) is one ... It contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. It is encoded by the PDCD1 gene, ... The PD1.3 monoclonal antibody recognizes T cells, activated CD4 and CD8 positive cells and activated B cells. This antibody has ...
However, newer treatments have shifted attention to targets on immune cells, resulting in dramatic responses. The effect of DNA ... Historically the development of anticancer treatments has been focused on their effect on tumor cells alone. ... Costimulatory receptor agonists or antagonists of inhibitory signals augment antigen-specific T-cell responses [133]. ... PD-1 is a transmembrane inhibitory coreceptor. Expression of PD-1 on T-cells and PD-L1 ligand interaction has been shown to ...
We estimated the expression of these costimulatory and inhibitory receptors on ICOS−/− T cells. PBMCs from controls and ... B and D, Pooled data on IFN-γ-producing cells among PBMCs, CD4 T cells, CD4+CD45RO+ cells, CD4+CD45RA+ cells, CD8 T cells, and ... CD4 T cells among CD4 T cells and that of PD-1+ CD8 T cells among CD8 T cells from HC and ICOS-deficient patients (1 and 2) ... ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409: 97-101. ...
However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to ... However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to ... Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector ... Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector ...
The NK cell-mediated killing is controlled by inhibitory, costimulatory, and lysis receptors (2). The main lysis receptors ... The killing of .221/Cw4-infected cells is influenced by the balance between inhibitory and activating receptors. The NK cells ... The NK cell cytotoxic activity is regulated by both inhibitory and activating NK receptors. Thus, changes in the expression ... The activity of NK cells is balanced by inhibitory and killing receptors (2), and killing will occur only if the killing ...
The diversity of costimulatory and inhibitory receptor pathways and the regulation of antiviral T cell responses. Curr Opin ... we wondered whether these cells expressed the inhibitory receptor PD-1, a marker of impaired T cells. In naive mice, less than ... Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1 ... Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells ...
Co-Stimulatory and Co-Inhibitory Receptor-Ligand Pairs. Vincenzo Cerundolo, University of Oxford, UK Harnessing NKT cells in ... Adoptive cell transfer (ACT) of anti-tumor T cells after the depletion host immune cells causes objective regression in about ... Exploiting T Cell Receptor Genes for Cancer Immunotherapy. Michel Sadelain, Memorial Sloan Kettering Cancer Center, USA Novel ... Potentials of T Cell Homeostatic Cytokines. Yang Liu, University of Michigan, Ann Arbor, USA Short Talk: CD24 Controls T Cell ...
... which inhibit T cell activation. This is the case of the T cell inhibitory receptor PD-1 ligand, PD-L1 [74-78]. PD-L2 is a ... tolerogenic DCs upregulate the surface expression of inhibitory costimulatory molecules, ... "Tumor cells convert immature myeloid dendritic cells into TGF-β-secreting cells inducing CD4+CD25+ regulatory T cell ... These T cells exert their cytotoxic activities towards transgene-expressing cells. Therefore, to avoid T cell responses, the ...
Expression of costimulatory and inhibitory receptors in FoxP3+ regulatory T cells within the tumor microenvironment: ... Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001. Review. ... Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells. ... Dynamic Imprinting of the Treg Cell-Specific Epigenetic Signature in Developing Thymic Regulatory T Cells. ...
The immune system is tightly controlled by co-stimulatory and co-inhibitory ligands and receptors. These molecules provide not ... T cell subsets (see total CD4+ T cells or Foxp3− naive T cells and Foxp3+ nTreg cells and memory CD4+ T cells), whereas CD8+ T ... ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature. 409:97-101. doi:10.1038/35051100. ... of cells were apoptotic in the presence of control-Ig. Similarly, of the cells within the live cell R1 gate, ∼72.6% cells ...
TILs express a wide range of co-inhibitory and co-stimulatory receptors. (A and B) Gene expression profile of cell surface ... which revealed expression of a broad panel of both inhibitory receptors and co-stimulatory receptors. These approaches have ... Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10:29-37. ... Moreover, the additional co-stimulatory and co-inhibitory receptors identified in our current work could represent functionally ...
ICOS is a CD28-like costimulatory receptor with a unique B7-like ligand. PD-1 is an inhibitory receptor, with two B7-like ... T cell activation is dependent upon signals delivered through the antigen-specific T cell receptor and accessory receptors on ... Integration of signals through this family of costimulatory and inhibitory receptors and their ligands is critical for ... the T cell. A primary costimulatory signal is delivered through the CD28 receptor after engagement of its ligands, B7-1 (CD80) ...
However, these agents typically function by activating costimulatory receptors (e.g., Ox40, Glucocorticoid induced TNF receptor ... which block key inhibitory pathways involved in T cell activation, have shown significant clinical potential in a number of ... No significant differences were observed for CD45+ cells, CD103+ DCs, total CD11c+ DCs, CD8+ T cells, CD4+ T cells, or NK cells ... Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 31, ...
T cells become activated if their T cell receptors recognize and bind the antigen on MHC complexes and their CD28 costimulatory ... inhibitory cell types such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells ( ... Other cell types, such as B cells, myeloid dendritic cells, mast cells, and Langerhans cells, can also express PD-1 which may ... 1) Upon T cell activation, the extracellular receptors PD-1, CD28, and the T cell receptor (TCR) complex (including CD4 or CD8 ...
... depletion decreases the expression of costimulatory molecules and increases the expression of the inhibitory receptors ILT3 and ... HLA-G act through the inhibitory receptors ILT2 and ILT4 expressed by myeloid DCs, CD4+ and CD8+ T cells, B cells, monocytes/ ... The chemokine CCL2 interacts with CCR2 receptor expressed by myeloid cells and NK cells, activated Th1 and Th17 cells, and ... cell-cell contacts involving NK cell activation receptor NKG2D, and membrane-bound TGFβ [205]. The role for MDSCs in the ...
Activation of T cells is opposed by inhibitory receptors, such as CTLA-4. These receptors can block many early activation ... 1⇓a). In T cells, ligation of the costimulatory receptor CD28 similarly activates the PI3K/Akt pathway (15), marking CD28 as a ... Ligation of the T cell co-stimulatory receptor CD28 activates the serine-threonine protein kinase protein kinase B. Eur. J. ... and costimulatory receptors (signal 2), which inform the T cell of the presence of an inflammatory environment. Although lectin ...
First, TIGIT is an inhibitory counterpart of the co-stimulatory receptor CD226. When TIGIT is present on the surface of ... Highest expression levels are observed on effector CD4+ and CD8+ T cells, regulatory T cells, and NK cells. TIGIT has several ... The assay consists of two genetically engineered cell lines:. TIGIT Effector Cells: Jurkat T cells expressing human TIGIT with ... The bioassay consists of two genetically engineered cell lines, TIGIT Effector Cells and CD155 aAPC/CHO-K1 Cells. Panel A. When ...
Hence, in this review we have highlighted and interlinked molecular signaling from cytokines, surface receptors, transcription ... Tfh cells are also generated from the conversion of other effector T cells as exemplified by Th1 cells converting into Tfh ... Tfh cells are also generated from the conversion of other effector T cells as exemplified by Th1 cells converting into Tfh ... cells help is critical for activation of B cells, antibody class switching and germinal center formation. The Tfh cells are ...
Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat. Immunol. 2002. 3: ... and ILT4 receptors expressed on the DCs. APCs tolerized by CD8+ T cells show reduced expression of costimulatory molecules and ... T cells, NKT cells, TCR γδ cells, or TCR αβ cells (80, 81). Only mice that were deficient in CD4+ αβ T cells developed EAE. ... T cell vaccination induces T cell receptor Vbeta-specific Qa-1- restricted regulatory CD8(+) T cells. Proc. Natl. Acad. Sci. U ...
... chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together ... expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific ... As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic ... The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3−. ...
  • The defective polarization into effector cells was associated with impaired induction of T-bet, GATA3, MAF, and retinoic acid-related orphan nuclear hormone receptor (RORC). (jimmunol.org)
  • Signaling by means of this receptor leads to recruitment and phosphorylation of an SH2 domain containing inositol polyphosphate 5′ phosphatase that regulates signaling by activating receptors ( 11 , 12 ). (pnas.org)
  • Here, we show that in TCR signaling, the scaffolding adapter Gab2 delivers an inhibitory signal via PI3K. (jimmunol.org)
  • Our findings provide the first evidence of a negative function for a scaffolding adapter in T cells and identify Gab2/PI3K-containing complexes as novel regulators of TCR signaling. (jimmunol.org)
  • However, the role of PI3K in T cell signaling on TCR engagement has remained confusing. (jimmunol.org)
  • Although both Siglec-G and CD22 are expressed on B cells and are able to inhibit BCR mediated signaling, they also show unique biological functions. (frontiersin.org)
  • Both Siglec-G and CD22 have also recently been linked to toll-like receptor signaling and may provide a link in the regulation of the adaptive and innate immune response of B cells. (frontiersin.org)
  • Recognition of antigen by the B cell antigen receptor (BCR) is the main event in the B cell immune response and signaling through the BCR complex is tightly regulated by several different co-receptors. (frontiersin.org)
  • CD22 and Siglec-G are two members of the Siglec (sialic acid-binding immunoglobulin-like lectins) family and have been shown to negatively regulate B cell signaling. (frontiersin.org)
  • The T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the α and β chains, and a signaling subunit, namely the CD3ε, γ and δ chains and the TCRζ chain. (wikipathways.org)
  • AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. (nih.gov)
  • This symposium will discuss the importance of cellular senescence and immune signaling in IPF as well as the roles of endothelial cells and alveolar epithelial cells, which are emerging as key drivers of disease. (nyas.org)
  • CD5 modulates signaling through the antigen-specific receptor complex (TCR and BCR). (selectscience.net)
  • To that end, we generated mice in which IL-10 signaling is specifically blocked in T cells by transgenic (TG) overexpression of a dominant-negative IL-10Rα under the CD4 promoter (CD4dnIL-10Rα mice). (rupress.org)
  • We found that IL-10 signaling in T cells is dispensable for the maintenance of the immune homeostasis in mice kept under specific pathogen-free conditions. (rupress.org)
  • We therefore conclude that the EMPD of human mIgE is a key control element of apoptotic signaling delivered through engagement of εBCR within the context of a mature B cell. (jimmunol.org)
  • In addition, the EMPD has been implicated in the different apoptotic signaling observed for IgM and IgD ( 14 ) and, in particular for IgE, the short EMPD isoform was apoptotic in the immature B cell line WEHI-231, while the long was not ( 12 ). (jimmunol.org)
  • In comparison with CD8 + RORγt − T cells, the CD8 + RORγt + T cells had a higher level of TCR signaling and were terminally differentiated and exhausted. (jimmunol.org)
  • The kinetic-segregation model might be applied to both co-receptor dependent and co-receptor independent signaling through TCR. (wikipedia.org)
  • According to the primary mechanism they propose for signal transduction and the fate of TCR/CD3 complex in T-cell triggering, the TCR signaling models might be divided into three basic categories. (wikipedia.org)
  • It is involved in cellular adhesion and costimulatory signaling. (wikipedia.org)
  • There are two types of NTs: Concentrative nucleoside transporters (CNTs): Na+-dependent symporters Equilibrative nucleoside transporters (ENTs): Na+-independent passive transporters The extracellular concentration of adenosine can be regulated by NTs, possibly in the form of a feedback loop connecting receptor signaling with transporter function. (wikipedia.org)
  • However, less is known about the expression of different co-inhibitory receptors on virus-specific CD4+ T cells mainly due to technical reasons since virus-specific CD4+ T cells have a lower frequency than virus-specific CD8+ T cells in the peripheral blood 1 , 15 . (nature.com)
  • While many studies have examined the role of circulating peripheral blood (PB) CD56+ NK cells, little is known about the resident CD56+ cell population. (deepdyve.com)
  • At the same time, positively selected thymocytes undergo an expansion phase that may act to increase numbers of T cells to aid the establishment of the peripheral T cell pool ( 6 ). (jimmunol.org)
  • The detection of IGRP-reactive T cells in both type 1 diabetic subjects and healthy subjects and recent reports of other autoreactive T cells detected in healthy subjects underscore the prevalence of potentially autoreactive T cells in the peripheral immune system of the general population. (jove.com)
  • In humans, MAIT cells are abundant in peripheral blood and liver, are uniformly memory and display a tissue-targeted phenotype , . (prolekare.cz)
  • Phenotypic studies examining Treg frequency in peripheral blood have showed similar proportions of these cells in patients who developed TB-IRIS and those who did not. (bloodjournal.org)
  • Natural killer (NK) cells comprise 5% to 20% of human peripheral blood lymphoid cells and are a critical component of the immune system, providing protection against viral infections and contributing to tumor immune surveillance. (bloodjournal.org)
  • citation needed]10 Additionally, patients with a chronic HCV infection were shown to have higher counts of Treg cells in peripheral blood when compared with successfully treated or healthy controls. (wikipedia.org)
  • These memory T cells lack lymph node-homing receptors and are thus found in the peripheral circulation and tissues. (wikipedia.org)
  • Thus, although this population as a whole is abundant within the peripheral circulation, individual virtual memory T cell clones reside at relatively low frequencies. (wikipedia.org)
  • A more detailed study has been hampered by a lack of cell surface markers defining tumor-specific dysfunctional TILs, and PD-1 alone is not sufficient. (rupress.org)
  • alternatively, immune cells can be genetically engineered to express a tumor-specific receptor, cultured and returned to the patient. (wikipedia.org)