BCL-2 BLOCKS DEGRANULATION BUT NOT FAS-BASED CELL-MEDIATED CYTOTOXICITY

The ability of bcl-2 in target cells to block cell-mediated cytotoxici ty by allospecific CTL was tested. The blocking effect was variable. B ecause killing by CTL involves two different pathways, degranulation ( perforin plus granzymes) and fas, we examined the effect of bcl-2 on t hese pathways independently. Bcl-2 in target cells blocked apoptotic c ell death induced either by cytotoxic granule extracts or by CTL killi ng under conditions in which the fas pathway is blocked. On the other hand, bcl-2 had no effect on target cell-killing either by Fas-specifi c mAb or by CTL capable of killing only via the fas pathway. These dat a suggest bcl-2 may block apoptotic lysis induced by perforin plus gra nzymes, but not apoptotic lysis induced via the fas pathway. Thus, any analysis of the effect of bcl-2 on apoptotic cell death in target cel ls killed by CTL must take into account the relative contributions of the degranulation vs fas pathways.