Abstract
The T cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. The T cell repertoire must be carefully regulated to prevent unwanted responses to self. In the periphery, one important level of regulation is the action of costimulatory signals in concert with T cell antigen-receptor (TCR) signals to promote full T cell activation. The past few years have revealed that costimulation is quite complex, involving an integration of activating signals and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR signals to determine the outcome of a T cell's encounter with antigen. Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. This review primarily focuses on the cellular and molecular mechanisms of regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Abatacept
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Adenocarcinoma / immunology
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Adenocarcinoma / therapy
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Amino Acid Motifs
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Animals
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use
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Antigens, CD
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Antigens, Differentiation / genetics
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Antigens, Differentiation / immunology*
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CD28 Antigens / immunology
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CTLA-4 Antigen
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Cell Cycle / physiology
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Cell Differentiation
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Clonal Anergy
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Cytokines / physiology
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Female
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Humans
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Immune Tolerance / immunology
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Immunoconjugates*
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Immunotherapy*
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Lymphocyte Activation
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Lymphoproliferative Disorders / genetics
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Macromolecular Substances
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Male
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Mammary Neoplasms, Experimental / immunology
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Mammary Neoplasms, Experimental / therapy
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Melanoma, Experimental / immunology
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Melanoma, Experimental / therapy
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Mice
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Mice, Knockout
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Models, Immunological
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Neoplasms / immunology
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Neoplasms / therapy*
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / therapy
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Receptors, Antigen, T-Cell / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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CD28 Antigens
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CTLA-4 Antigen
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CTLA4 protein, human
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Ctla4 protein, mouse
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Cytokines
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Immunoconjugates
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Macromolecular Substances
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Receptors, Antigen, T-Cell
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Abatacept