CTLA-4 blockade of antigen-induced cell death

While cytotoxic T lymphocyte antigen-4 (CTLA-4) negatively regulates T-cell receptor (TCR)-driven interleukin (IL)-2 production and proliferation, lit tle is known regarding whether the coreceptor has the capacity to inhibit o ther events, such as Fas ligand (FasL) expression and antigen- induced cell death (AICD), In this study, it is shown that CTLA-4 expressed in a T-cell hybridoma can elicit a potent block of fasL expression end AICD, Inhibitio n occurred independently of CTLA-4 blockage of IL-2 production and was part ially reversed by a single mutation in the cytoplasmic YVKM motif. These fi ndings indicate that CTLA-4 can block TCR signaling prior to bifurcation of signals leading to IL-2 production end apoptosis.