Liver inflammatory injury induced by IR and therefore indicated another mechanism of clinical good performance of anti-CD25 mAb in transplantations besides organ tolerance induction. Liver ischemia-reperfusion injury occurs in the clinical settings of hepatic resection surgery, hemorrhagic trauma, and liver transplantation. In the last 20 years, the rates of acute and chronic rejection have fallen dramatically, for example, the incidence of acute rejection during the first six months post-transplant has declined from over 40% in 1995 to around 15% in 2000. Part of this improvement results from increased use of selective induction agents, particularly the interleukin-2 receptor antagonists. Addition of anti-CD25 mAb to a variety of calcineurin inhibitor-based immunosuppressive regimens reduced acute rejection by 30�C50% as reported in two meta-analyses of the randomized controlled trials. These meta-analyses also demonstrated trends toward improved graft survival with anti-CD25 mAb compared with no induction. Although the protective effect for induction therapy of anti-CD25 mAb has been widely documented in liver transplantation field, the exact effect of anti-CD25 mAb on liver IR injury, however, remains poorly elucidated. The present study for the first time demonstrated that antiCD25 mAb administration shortly antecedent to liver IR induction provides protection in the initiation phase of injury. After 70% liver ischemia, anti-CD25 mAb pretreated mice displayed Ascomycin significantly preserved liver function as characterized by less histological damage and reduced serum enzymes level. We further demonstrated that the protective effect was associated with ameliorated intrahepatic inflammatory milieu and reduced CD4 + T lymphocytes as manifested by the decrease of Metyrapone proinflammatory cytokine production and the lower CD4/CD8 proportion. By employing an in vitro lymphocytes proliferation assay model, we confirmed that the protective effect of near-term antecedent anti-CD25 mAb treatment on IR-induced liver injury depend on the inhibition on the proliferation of CD4 + T lymphocytes. Taken together, our data demonstrated that near-term antecedent anti-CD25 mAb treatment provides protection for livers against subsequent IRinduced injury by inhibiting the proliferation of CD4 + T lymphocytes and mitigates intrahepatic inflammatory milieu through decreasing the proinflammatory cytokine production. Our data presented in the current report are in agreement with previous studies in the lung, kidney and brain after IR induction. 
These results suggested that this brisk response, which preceded the influx of innate immune cells to the injured tissue, is mainly associated with resident T lymphocytes. These organ-resident T lymphocytes can maintain the expression of specific cytokine receptor on their cell surface and proliferate in vivo in the absence of Ag stimulation. It has been previously demonstrated that use of MHC-IIblocking antibodies has no effect on serum alanine transaminase following hepatic IR, which suggested that T cells play a role not involving the ab TCR and that lymphocyte actions occur through a non-antigenic mechanism. Treg is known as a critical role in maintaining immune homeostasis. In the model of IR injury, Treg functions to restrain excessive Teff cell responses. In line with the studies of depletion kinetics of PC61, the near-term administration of PC61 did not modify the number of Tregs significantly, and the depletion of CD4 + FoxP3 + Tregs in PC61-treated mice was already apparent 4 days after injection.