Induction of immune tolerance by pre-infusion of apoptotic lymphocytes derived from peripheral blood of donor rats before liver transplantation.

ABSTRACT

AIM: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find an effective method for preventing acute rejection. The aim of this study was to investigate the effects of immune tolerance by pre-infusion of apoptotic lymphocytes derived from peripheral blood of donor rats before liver transplantation. METHODS: By using male Wistar and Sprague-Dawley (SD) rats as liver donors and recipients, an orthotopic liver transplantation model was established. The rats were divided into Group A (control group) and Group B (apoptotic lymphocytes pre-infusion group). In group B, 1ml apoptotic lymphocytes suspension (concentration 5×107 cells/mL) which were irradiated by X-ray from electron linear accelerator at the absorbed dose of 2.0Gy was pre-infused via the deep dorsal vein of penis on the 7th day before operation. The serum alanine transaminase (ALT), total bilirubin (TBIL), the serum of interleukin (IL) including IL-2, IL-4 and IL-10, liver pathological changes, and survival time were analysed. RESULTS: The survival in Group A were 7~13d, with the median survival time (MST) of 11d, and in Group B were 37~60 d, with the MST of 60 d. There were significant differences between the two groups in survival (P <0.001). There were significant differences between the two groups in ALT (P <0.01) and TBIL (P <0.01). Microscopic inspection revealed that severe acute rejection in the Group A, but no sign of acute rejection was observed in the Group B in the 7th day postoperation. The levels of IL-2 were increased after operation in two groups, but was obviously increased in the 7th (P <0.01) and 10th (P <0.001) day postoperation in Group A. The levels of IL-4 and IL-10 in Group A were declined but were increased in the 7th (P <0.01) and 10th (P <0.001) day postoperation in Group B. CONCLUSION: Preinfusion of apoptotic lymphocytes derived from peripheral blood of donor rats can induce immune tolerance in liver transplantation. Increased expression of Th2 cytokines (IL-4 and IL-10) may plays an important role in inducing immune tolerance.