Target cell lysis by cytotoxic T lymphocytes that lack detectable hemolytic perforin activity

When mouse target cells are subjected to cytolytic attack by mouse CTL cell lines that have been cultured for many months in high levels of IL-2, and have abundant perforin-rich secretory granules, they exhibit two prominent changes: 1) rapid and massive increase (greater than 10-fold) in intracellular Ca2+ concentration and 2) fragmentation of DNA into nucleosome-sized fragments. We show here that when the same target cells are subjected to cytolytic attack by perforin-deficient CTL, either human CTL or primary mouse CTL from peritoneal exudates, the same changes are observed, suggesting that perforin-rich and perforin-deficient CTL kill their target cells by similar (if not identical) mechanisms. It is possible that perforin-deficient CTL produce enough perforin to destroy target cells but not enough to be detected by currently available methods.