FAS-MEDIATED CYTOTOXICITY - AN IMMUNOEFFECTOR OR IMMUNOREGULATORY PATHWAY IN T-CELL-MEDIATED IMMUNE-RESPONSES

Fas/Fas ligand interactions serve as a signaling pathway for apoptosis (1-3), an important regulatory mechanism in the development and funct ion of the immune system (4-9). Recent evidence that Fas-dependent apo ptosis is also an important mode of T cell cytotoxicity (10-13) sugges ted that Fas might play a critical role in the effector phase of T-dep endent immune responses, such as allograft rejection. We observed that Fas transcripts are constitutively expressed in syngeneic and allogen eic murine cardiac transplants, while Fas ligand (Fast) is up-regulate d only in rejecting allografts. Surprisingly, the absence of an intact Fas/FasL pathway did not alter the tempo of allograft rejection, even CD4-dependent rejection. These results indicate that Fas/FasL interac tions are not essential mediators of T cell-induced allograft damage. Rather, as suggested in other studies, the Fas pathway may be principa lly involved in the regulation of clonal expansion and subsequent cont raction of T cell populations during immune responses.