REGULATION OF THE FAS LYTIC PATHWAY IN CLONED CTL

Cloned murine CTL activated via the TCR or by PMA and ionomycin up-reg ulate surface Fas ligand and show an increased ability to kill non-Ag- specific Fas(+) target cells. This up-regulation starts after 45 to 60 min and has a t(1/2) for reversal of about 90 min. Up-regulation of l ytic function is accompanied by up-regulation of Fas ligand on the CTL surface, which can be blocked by protein synthesis inhibitors. When u p-regulation of Fas lytic function was induced by PMA and ionomycin, E GTA blocked both activation of lytic function and expression of Fas li gand detected by FACS analysis. However, when up-regulation was induce d by specific Ag, EGTA blocked activation of lytic function, but not u p-regulation of Fas ligand. Moreover, EL-4 cells have very high levels of surface Fas ligand, although they are not cytotoxic. Thus, express ion of surface Fas ligand may be required, but not sufficient, for Fas -mediated lysis.