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-de pendent immune responses are initiated and subsequently regulated. Ligation of the TCR with an antigenic peptide bound to an MHC protein on a professi onal APC provides the crucial antigen-specific stimulus required for T cell activation. Interaction of CD28 with CD80 or CD86 molecules on APC initiat es a costimulatory or second signal within the T cell which augments and su stains T cell activation initiated through the TCR. However, recently it ha s become clear that T cell immune responses are a result of a balance betwe en stimulatory and inhibitory signals. Cytotoxic T lymphocyte-associated mo lecule-4 (CTLA-4) is a cell surface molecule that is expressed nearly exclu sively 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.