T-CELL RECEPTOR SIGNALS ENHANCE SUSCEPTIBILITY TO FAS-MEDIATED APOPTOSIS

Fas(CD95) and its Ligand (Fast) interaction plays a pivotal role in T cell receptor (TCR)-mediated apoptosis. However, the susceptibility of T cells to Fas-mediated apoptosis is tightly regulated during immune responses, a regulation which is thought to maintain the antigen-speci ficity of T cell apoptosis. Here we show that TCR stimulation enhances the induction of Fas-mediated apoptosis. In addition, using a mutant T cell hybridoma with impaired Fast expression, we show that the syner gy provided by TCR stimulation can be mimicked by activators of PKC bu t not calcium influx. This effect cannot be inhibited by actinomycin D , suggesting that TCR stimulation leads to the alteration in preexisti ng signaling molecules to enhance Fas-mediated apoptosis. Our results therefore provide a mechanism of how Fas-FasL interactions lead to T c ell death in an antigen-specific manner via repetitive antigen stimula tion.