Exocytosis of cytolytic granules may not be required for target cell lysis by cytotoxic T-lymphocytes.

Secretory processes have been implicated in the mechanism of target-cell lysis by cytotoxic T-lymphocytes (CTL) (refs 1, 2). Both CTL and cytotoxic large granular lymphocytes have cytolytic granules, containing the cytolytic molecules 'perforin' and 'cytolysin'; perforin and cytotoxic lymphocytes can damage target cells through the membrane assembly of pores. The description of proteases which are cytotoxic cell-associated and granule-located has supported the granule exocytosis model of cytotoxicity mediated by cytotoxic lymphocytes, and has emphasized the similarities between cell-mediated and complement-mediated cytotoxicity. But recent experiments have challenged the importance of lytic granules and perforin in CTL activity. Here we report that CTL can be triggered to deliver a lethal hit to target cells even when exocytosis of lytic granules has been abolished by removal of extracellular calcium. This dissociation of exocytosis of granules and delivery of the lethal hit suggests that cytolytic granules may not be involved in target-cell lysis by CTL.