Crucial Fas-Fas ligand interaction in spontaneous acceptance of hepatic allografts in mice.

The Fas/Fas ligand (FasL) system plays important roles in the immune system, including host immunoregulation and cytotoxicity. In this study, we investigated the involvement of Fas-FasL interactions in spontaneous acceptance of hepatic allografts in murine orthotopic liver transplantation. Liver transplantation between the C57BL/6 (B6, H-2b) donor and the MRL/Mp (MRL, H-2k) recipient was performed in various combinations of donor and recipient mice with wild type (+/+), Fas-mutant (lpr) or FasL-mutant (gld) genotypes. The prolongation and spontaneous acceptance of the fully allogeneic grafts in recipients was not observed in either MRL-lpr recipients with B6+/+ livers or MRL+/+ recipients with B6-gld livers. Moreover, the serum alanine aminotransferase (ALT) levels and the degree of cell infiltration into hepatic allografts on day 7 after transplantation were inversely correlated with the recipient survival time (in days). The donor-specific cytotoxic T-lymphocyte (CTL) activities of the graft-infiltrating cells (GICs) from MRL-gld recipients with B6+/+ livers were much lower than those from MRL+/+ or -lpr recipients on days 5 and 10 after transplantation. However, the CTL activities of the GICs from MRL+/+ and -gld recipients predominantly disappeared by day 15 after transplantation. Furthermore, the anti-donor CTL activities induced in MRL+/+ recipients were ascribed to CD8+ cells, and were not mediated by Fas-FasL interactions. These results strongly suggest that the Fas/FasL system plays a critical role for recipient immunoregulation, enabling recipients in accepting hepatic allografts by deletion of the donor-specific T cells, but not for CTL/target cell interaction in MRL+/+ recipients.