title: Induction of immune tolerance by pre-infusion of apoptotic lymphocytes derived from peripheral blood of donor rats before liver transplantation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, China. Jifzhejiang@gmail.com
authors.forename: J F
authors.initials: JF
authors.lastname: Feng
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D001663:Bilirubin / Q000097:blood; D006084:Graft Rejection / Q000517:prevention & control; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D007262:Infusions, Intravenous; D007378:Interleukins / Q000097:blood; D016031:Liver Transplantation; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects; D008297:Male; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014019:Tissue Donors
chemical_list: D007378:Interleukins; D000410:Alanine Transaminase; D001663:Bilirubin