Cytotoxic T cells specifically induce Fas on target cells, thereby facilitating exocytosis-independent induction of apoptosis

Cytotoxic T (Tc) cells deficient in perforin lyse Fas-negative targets after lengthy incubation periods. This process is independent of granzymes, and killing occurs via the Pas pathway for the following reasons. Interaction of perforin-deficient Tc cells with Pas-negative targets leads to an up-regulation of Pas that is dependent on Ag recognition, de novo synthesis, and transport of proteins to the target cell surface. Treatment of effecters with brefeldin A, but not with the exocytosis inhibitor concanamycin, inhibited this process. Lysis of targets is inhibited by anti-Pas Abs, soluble mouse Pas-Pc, and the caspase-cascade inhibitor, crm-A, Targets from Pas-mutant lpr mice are refractory to lysis, and Tc cells from mice deficient in Fas- and perforin-mediated lysis do not lyse Pas-negative targets. The possible relevance of this exocytosis-independent cytolytic process in the regulation of T cell activity and control of pathogens is discussed.