CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy

Annu Rev Immunol. 2001;19:565-94. doi: 10.1146/annurev.immunol.19.1.565.

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

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abatacept
  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy
  • Amino Acid Motifs
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • CD28 Antigens / immunology
  • CTLA-4 Antigen
  • Cell Cycle / physiology
  • Cell Differentiation
  • Clonal Anergy
  • Cytokines / physiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Humans
  • Immune Tolerance / immunology
  • Immunoconjugates*
  • Immunotherapy*
  • Lymphocyte Activation
  • Lymphoproliferative Disorders / genetics
  • Macromolecular Substances
  • Male
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / therapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Knockout
  • Models, Immunological
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Cytokines
  • Immunoconjugates
  • Macromolecular Substances
  • Receptors, Antigen, T-Cell
  • Abatacept