Lymphocyte activation: T-cell regulation by CTLA-4

The initiation of immune responses usually requires interactions of T lymphocytes with antigen-presenting cells. The specificity of these interactions depends on the recognition by the T cell’s antigen receptor of an antigenic peptide presented in a complex with molecules of the major histocompatibility complex (MHC). But a successful immune response requires additional costimulation of the T cell by molecules on the antigen-presenting cell. Notable amongst such costimulatory molecules are those of the B7 family, CD80 and CD86. These two molecules each bind to the T-cell receptors CD28 and CTLA-4 (cytotoxic T lymphocyte-associated molecule-4) and trigger cytokine production and activation of the T cell. Although the overall response to stimulation by the B7 family is strong activation, it has recently become apparent that triggering CTLA-4 has inherently different effects on T-cell activation than does triggering CD28 (reviewed in [1,2]). Here we discuss recent developments showing that CTLA-4 is an important negative regulator of T-cell activation.