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Fas‐based lymphocyte‐mediated cytotoxicity against syngeneic activated lymphocytes: A regulatory pathway?

To investigate the possibility that Fas‐based immune regulation and Fas‐based T cell‐mediated cytotoxicity (F‐CMC) are causally related, we explored the latter in activated lymphocyte populations. These were shown to contain effector cells exerting cytotoxicity via an F‐CMC mechanism which could be differentially triggered by PMA and ionomycin. F‐CMC operated in trans, requiring an lpr (Fas) product on target cells and a gld product on effector cells. Activated lymphocyte populations were also shown to contain F‐CMC target cells. Activated lymphocyte populations thus contained both effector and target F‐CMC cells, which could lyse each other. Fas‐based cytotoxicity can thus lead to the lysis of syngeneic activated lymphocytes, consistent with the possibility of its participation in the down‐regulation of immune responses, and more generally offering a model of socially controlled, direct membrane‐mediated cell death.