Role of the CTLA-4 receptor in T cell activation and immunity. Physiologic function of the CTLA-4 receptor.

Costimulatory molecules of the B7 family regulate the activation of T lymphocytes. T cell activation is promoted by binding of B7 molecules to CD28 and inhibited by binding to CTLA-4 (CD152). The balance between positive signals through CD28 and negative signals through CTLA-4 is critical for the fate of the T cell and is subject to tight regulation. Recent in vitro and in vivo studies have significantly advanced our understanding of the function of the CTLA-4 receptor. The results of these experiments suggest that CTLA-4 is critical for the induction of self-tolerance, and that it may have distinct signaling functions in resting and activated T cells. In resting T cells, CTLA-4 crosslinking leads to cell-cycle arrest, whereas in activated T cells, CTLA-4 crosslinking induces apoptosis. In this article, we will review the physiologic functions of the CTLA-4 receptor.