IDO-Competent-DCs Induced by IFN-γ Attenuate Acute Rejection in rat Liver Transplantation
BACKGROUND Costimulation between the glucocorticoid-induced tumor necrosis factor receptor and its ligand (GITRL) breaks immunologic tolerance induced by regulatory T cells. The purpose of this research was to examine the involvement of GITRL during rat liver transplantation, the survival of which depends on interactions between regulatory T cells and Kupffer cells (KCs). METHODS Recipients were divided into 2 groups: The allograft group underwent orthotopic liver transplantation from male Lewis to Brown Norway (BN) rats and the isograft group, BN-to-BN liver transplantation. We evaluated 2-week survival rates, histologic changes, as well as serum and supernatant levels of tumor necrosis factor-α (TNF-α); GITRL, and TNF-α expressions in the graft, and GITRL expression by graft-derived KCs. RESULTS TNF-α levels were increased in plasma and in the supernates of KCs during allograft transplantation compared with isograft liver transplantation (P <.05). The expressions of TNF-α and GITRL in liver grafts were increased during acute rejection. Furthermore, the expression of GITRL on KCs derived from allografts was increased compared with isografts (P < .05). CONCLUSION GITRL expression on KCs may mediate acute rejection in liver transplantation.