INVOLVEMENT OF 2 DISTINCT KILLING MECHANISMS IN BYSTANDER TARGET-CELLLYSIS INDUCED BY A CYTOTOXIC T-LYMPHOCYTE CLONE

Cytotoxic T lymphocyte (CTL) can lyse target cells by mainly two diffe rent mechanisms including granule exocytosis- and Fas-based cytotoxici ty. In addition, CTL also lyse bystander target cells. In this study, we examined whether these two different killing mechanisms also cause bystander target cells lysis. EL-4 cells, representing bystander targe t cells, were incubated with CD8(+) CTL clone B7B7 and antigen-treated P815 cells. EGTA-MgCl2 inhibited bystander lysis and reduced the rele ase of BLT esterase. In addition, lysis of Fas-negative bystander cell s (thymocytes from C57BL/6J-lpr/lpr not expressing Fas antigen) was al so detected. CTL preactivated with antigen-treated P815 cells maintain ed a killing activity on bystander cells in the presence of cyclohexim ide (CHX). Furthermore, the presence of anti-Fas mAb inhibited the lys is of EL-4 cells by CTL stimulated with anti-TCR mAb. Thus, our result s suggest that granule exocytosis- and Fas-mediated signal pathways ca use the lysis of bystander target cells. (C) 1996 Academic Press, Inc.