Abstract
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.
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