The role of CTLA-4 in the regulation of T cell immune responses

Immunol Cell Biol. 1999 Feb;77(1):1-10. doi: 10.1046/j.1440-1711.1999.00795.x.


Over the past few years a great deal of research has examined how T cell-dependent immune responses are initiated and subsequently regulated. Ligation of the TCR with an antigenic peptide bound to an MHC protein on a professional APC provides the crucial antigen-specific stimulus required for T cell activation. Interaction of CD28 with CD80 or CD86 molecules on APC initiates a costimulatory or second signal within the T cell which augments and sustains T cell activation initiated through the TCR. However, recently it has become clear that T cell immune responses are a result of a balance between stimulatory and inhibitory signals. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface molecule that is expressed nearly exclusively on CD4+ and CD8+ T cells. Investigation into the role of CTLA-4 in the regulation of T cell immune responses has revealed that CTLA-4 is a very important molecule involved in the maintenance of T cell homeostasis. In the present review, evidence for the proposed inhibitory role of CTLA-4 is examined and a model suggesting a role for CTLA-4 in both early and late stages of T cell activation is presented.

Publication types

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

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen
  • Humans
  • Immune Tolerance
  • Immunoconjugates*
  • In Vitro Techniques
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Ligands
  • Abatacept