IL-1-BETA CONVERTASE (ICE) DOES NOT PLAY A REQUISITE ROLE IN APOPTOSIS INDUCED IN T-LYMPHOBLAST BY FAS-DEPENDENT OR FAS-INDEPENDENT CTL EFFECTOR MECHANISMS

Both IL-1 beta convertase (ICE) and other members of the ICE-like fami ly of proteases have been reported to play a role in Fas-mediated apop tosis. Con A-stimulated T lymphoblasts generated from splenocytes isol ated from ICE-deficient H-2(b) mice were found to be more susceptible than wild-type lymphoblasts to DNA fragmentation induced by H-2(b)-spe cific CTL derived from normal or Fas ligand-deficient gld/gld mice. Tr initrophenyl (TNP)-modified, H-2(b) target cell-specific CTL were gene rated from perforin-deficient mice and were found to induce DNA fragme ntation only in target cells expressing functional Fas receptors, Simi lar rates of DNA fragmentation were induced in TNP-modified ICE -/- an d ICE +/+ T lymphoblast targets by perforin -/- TNP-modified, H-2(b) t arget cell-specific CTL, In addition, anti-Fas Abs induced apoptosis i n thymocytes, Con A-stimulated spleen T cells, LPS-stimulated spleen B cells, and thymocytes from ICE -/- mice, However, DNA fragmentation i nduced by either allospecific Fast-defective CTL, or by perforin-defic ient, TNP-modified, H-2(b) target cell-specific CTL was prevented in I CE -/- target cells loaded by electroporation with Ac-DEVD-CHO, an inh ibitor of CPP32 and related ICE family proteases, These findings indic ate that ICE does not play a requisite role in Fas-dependent or Fas-in dependent mechanisms of apoptosis induced in peripheral T lymphoblasts by CTL, However, both major pathways of CTL-induced apoptosis appear to be dependent on the enzymatic activity of other ICE family protease s.