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

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.