Bystander apoptosis induced by CD8+ cytotoxic T cell (CTL) clones: implications for CTL lytic mechanisms

Cytotoxic T lymphocyte (CTL) mediated killing has classically been associated with a high level of specificity for the target cell. However, when CTL clones and specific target cells were copelleted with innocent bystander cells for which the CTL was not specific, these bystander cells were also lysed. Bystander lysis did not depend on HLA compatibility between effector and bystander cell. Indeed bystander lysis was particularly efficient during cognate synthetic peptide induced CTL-CTL killing. Bystander lysis was species unrestricted. Lytic activity could not be transferred in supernatants nor could it be inhibited by anti-tumor necrosis factor antibodies. Perforin sensitive red blood cells were very inefficiently bystander lysed. Bystander cell death was characterized by DNA fragmentation indicative of apoptosis or programmed cell death. Bystander lysis thus appeared to be due to the apoptotic CTL lytic mediator(s). Importantly, CTL were not resistant to bystander lysis induced by other CTL; nor did they become resistant when they were actively killing target cells. Since it is well established that CTL survive the delivery of their own lytic mediators, these results suggest that CTL induced apoptosis is a membrane mediated event.