Inducement of rat liver transplantation tolerance by Treg cells and imDCs / 中华器官移植杂志

ABSTRACT

Objective To explore the effects of combined infusion of Treg cells from recipient rats and imDCs from donor rats prolonging the survival time of rats undergoing allogeneic orthotopic liver transplantation.Methods One hundred cases of rat allogeneic orthotopic liver transplantation were performed by using modified two-cuff method: DA rats served as donors,and Lewis rats as recipients,which were divided into 5 groups acute rejection group,mDC group,imDC group,Treg group,co-infusion group (imDC-Treg group).2 × 106 imDC,2 × 106 mDC and 1 × 107 Treg cells were respectively injected to Lewis rats in every group via caudal vein before transplantation.Four Lewis rats from each group were randomly sacrificed on the day 3,7 and 10 after transplantation.Liver function (ALT and TBIL) and changes of cytokines (IL-10,IL-2 and TGF-β) were evaluated in peripheral blood.The pathological changes of the liver graft were observed.The DNA fragmentation characteristics of apoptosis in the liver were detected by using TUNEL staining.Survival analysis was performed on remnant rats.Results The liver function in imDC-Treg group had reverted to normal faster than that in the control groups.ELISA revealed that at day 7,the serum levels of IL-10 and TGF-β were higher,and the serum levels of IL-2 were lower in imDC-Treg group.Liver pathology demonstrated that there was only a slight number of mononuclear cell infiltration in hepatic graft afterorthotopic liver transplantation in co-infusion group (imDC-Treg group),which belonged to a nonidentified or slight type of acute rejection,and the liver graft showed regeneration of hepatocytes along with a small number of neutrophile granulocyte infiltration at the day 10.TUNEL staining indicated that the number of apoptotic T cells was much less in control groups than in imDC-Treg groups.The survival time of recipients in Treg-imDC group was 37 days,significantly longer than in irnDC group (23 days) and Treg group (15 days).Conclusion Infusion of imDC from donor rats or Treg from recipient rats alone couldn't induce long-term allograft survival of recipients after allogeneic rat liver transplantation.The co-infusion of Treg and imDC significantly prolonged the survival time of rats subject to allogeneic liver transplantation.