The Role of Cytoplasmic Granules in Cytotoxicity by Large Granular Lymphocytes and Cytotoxic T Lymphocytes
Three years ago, at the First Workshop on Mechansisms of Cell-Mediated Cytotoxicity, we presented a summary of the evidence developed in our lab that the ADCC and NK cytotoxic functions of large granular lymphocytes (LGL) operated via a secretory process (1). We showed by EM that for both NK and ADCC, target contact induces a rearrangement of the LGL cytoplasmic granules suggesting exocytosis. This secretion was evidenced by deposition of material which had been in the granules into the intracellular space, where 15 nm pore-like ring structures formed from this material. These structures were identical to those previously reported in a collaborative study with Dourmashkin (2), where they were seen on target membranes after ADCC. The pore-like structures were similar in appearance to those made by complement but had a larger diameter; these findings correlated nicely with molecular sieving experiments of markers released from red cell ghosts attacked by complement and by LGL in ADCC (3). Similar pore-like structures were reported to be associated with cytotoxicity by a cloned cell line with NK activity (4).
KeywordsNatural Killer Natural Killer Cell Lytic Activity Cytolytic Activity Percoll Gradient
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