The role of the perforin and Fas pathways of cytotoxicity in skin graft rejection

Cell-mediated cytotoxicity is believed to play an important role in the mechanisms of rejection following organ and tissue transplantation. We have investigated the role of the perforin and Fas pathways of cell-mediated cytotoxicity on the survival of xenogeneic, allogeneic and hemiallogeneic skin grafts. Wild type C57BL/6 (B6), perforin deficient C57BL/6 (B6 PKO) and Fas ligand deficient (B6 gld/gld) mice were grafted with xenogeneic Lewis rat skin grafts, or allogeneic B10.BR, class I disparate B6 bm1, class II disparate B6 bm12, and Fas deficient allogeneic C3H lpr/lpr grafts. No significant difference was observed in the timing of rejection with B6 PKO mice as recipients when compared with normal B6 controls. All grafts were also rejected by B6 gld/gld recipients, but with a significantly delayed pattern of rejection, showing, therefore, that Fas, although not critical, may participate to the mechanisms of rejection. Neither perforin nor Fas, however, seem to be essential for rejection of a skin graft, and it is likely that alternative mechanisms assume an important role in the effector phase of rejection once these cell-cytotoxic pathways are abrogated.