MAINTENANCE OF CLONOTYPE SPECIFICITY IN CD95 APO-1/FAS-MEDIATED APOPTOSIS OF MATURE T-LYMPHOCYTES/

Ag-induced mature T cell apoptosis is the result of death-inducing cyt okines, including the ligand for CD95 (Apo-1/Fas). This raises the pos sibility that expression of this death molecule could affect bystander T cells that were not directly antigenically stimulated but that expr ess the CD95 receptor. We show here that bystander T cells, even if th ey express the CD95 receptor, are not killed when exposed to T cells u ndergoing Ag-induced apoptosis. Rather, cell death is restricted to T cells that bear the receptor clonotype that is specifically engaged by TCR ligands. At least one mechanism of clonotype restriction is a sig nificant enhancement of CD95-induced apoptosis by TCR ligation. Our re sults demonstrate that, in addition to the well-known ability of TCR t o stimulate apoptosis by inducing CD95 ligand expression, TCR signals at the time of CD95 engagement can effectively increase apoptosis. The refore, we pot forward the hypothesis that strict clonotype specificit y is preserved when death cytokines such as CD95 ligand induce autoreg ulatory mature T cell apoptosis, at least in part through a sensitizat ion signal provided by the TCR stimulation.