Uchiyama Hideaki, Kishihara Kenji, Minagawa Ryosuke, Hashimoto Koji, Sugimachi Keizo, Nomoto Kikuo
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Immunology. 2002 Apr;105(4):450-7. doi: 10.1046/j.1365-2567.2002.01388.x.
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.
Fas/Fas配体（FasL）系统在免疫系统中发挥着重要作用，包括宿主免疫调节和细胞毒性。在本研究中，我们调查了Fas - FasL相互作用在小鼠原位肝移植中肝脏同种异体移植自发接受过程中的作用。将C57BL/6（B6，H - 2b）供体和MRL/Mp（MRL，H - 2k）受体之间进行肝移植，供体和受体小鼠具有野生型（+/+）、Fas突变型（lpr）或FasL突变型（gld）基因型的各种组合。在接受B6+/+肝脏的MRL - lpr受体或接受B6 - gld肝脏的MRL+/+受体中，均未观察到完全同种异体移植物在受体中的延长和自发接受。此外，移植后第7天血清丙氨酸转氨酶（ALT）水平和肝同种异体移植物中的细胞浸润程度与受体存活时间（以天为单位）呈负相关。移植后第5天和第10天，接受B6+/+肝脏的MRL - gld受体的移植物浸润细胞（GICs）的供体特异性细胞毒性T淋巴细胞（CTL）活性远低于MRL+/+或 - lpr受体。然而，移植后第15天，MRL+/+和 - gld受体的GICs的CTL活性主要消失。此外，在MRL+/+受体中诱导的抗供体CTL活性归因于CD8 +细胞，并且不是由Fas - FasL相互作用介导的。这些结果强烈表明，Fas/FasL系统在受体免疫调节中起关键作用，通过删除供体特异性T细胞使受体接受肝脏同种异体移植，但在MRL+/+受体的CTL/靶细胞相互作用中不起作用。
