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Crucial Fas–Fas ligand interaction in spontaneous acceptance of hepatic allografts in mice
Author(s) -
Uchiyama Hideaki,
Kishihara Kenji,
Minagawa Ryosuke,
Hashimoto Koji,
Sugimachi Keizo,
Nomoto Kikuo
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01388.x
Subject(s) - fas ligand , ctl* , cd8 , transplantation , cytotoxic t cell , immunology , immune system , liver transplantation , biology , immune tolerance , medicine , apoptosis , programmed cell death , in vitro , biochemistry
Summary 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‐2 b ) donor and the MRL/Mp (MRL, H‐2 k ) 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 predominately 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.