FAS AND ITS LIGAND IN A GENERAL MECHANISM OF T-CELL-MEDIATED CYTOTOXICITY

To investigate the mechanisms of T-cell-mediated cytotoxicity, we estimated the involvement of apoptosis-inducing Fas molecule on the target cells and its ligand on the effector cells. When redirected by ConA or anti-CD3 monoclonal antibody, a CD4(+) T-cell clone, BK1, could lyse the target cells expressing wild-type Fas molecule but not those expressing death signaling-deficient mutants. This indicates the involvement of Fas-mediated signal transduction in the target cell lysis by BK1. Anti-CD3-activated bat not resting BK1 expressed Fas ligand as detected by binding of a soluble Fas-Ig fusion protein, and the BK1-mediated cytotoxicity was blocked by the addition of Fas-Ig, implicating the inducible Fas ligand in the BK1 cytotoxicity. Ability to exert the Fas mediated cytotoxicity was not confined to BK1, but splenic CD4(+) T cells and, to a lesser extent, CD8(+) T cells could also exert the Fas-dependent target cell lysis. This indicates that the Fas-mediated target cell lytic pathway fan be generally involved in the T-cell-mediated cytotoxicity. Interestingly, CD4(+) T cells prepared from gld/gld mice did not mediate the Fas-mediated cytotoxicity, indicating defective expression of functional Fas ligand in gld mice.