Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model  

作　　者：ZHANG YeWei ZHAO HeWei BO Lin YANG YinXue LU Xiang SUN JingFeng WEN JianFei HE Xia YIN GuoWen 

机构地区：[1]Department of Hepatobiliary and Pancreatic Surgery,Affiliated Jiangsu Cancer Hospital of Nanjing Medical University,Nanjing 210009,China [2]Department of Rheumatism and Immunology,Affiliated No.2 Hospital of Suzhou University,Suzhou 215000,China [3]Department ofGeneral Surgery,Affiliated Hospital of Ningxia Medical University,Yinchuan 750004,China [4]Department of Geriatrics,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China [5]Department of Radiotherapy,Affiliated Jiangsu Cancer Hospital of Nanjing Medical University,Nanjing 210009,China [6]Department of lnterventional,Affiliated Jiangsu Cancer Hospital of Nanjing Medical University,Nanjing 210009,China

出　　处：《Science China(Life Sciences)》2012年第9期774-781,共8页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (Grant No. 61141013);the Key Medical Talents of Jiangsu Province(Grant No. RC2011090);the Natural Science Foundation of Jiangsu Province (Grant No. SBK201120268);the 333 Program for High Level Talents of Jiangsu Province (Grant No. 2011III-2640)

摘　　要：Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4＋CD25＋ regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were re- cipients. Rats were randomly assigned to the following four groups： control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3＋CD4＋CD25＋ regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body in＇adiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased signifi- cantly to （459.2±76.9） U L^- 1, total bilirubin increased to （124.1±33.7） μmol L-1 （P〈0.05） and the ratio of Foxp3＋CD4＋CD25＋ regulatory T cells decreased significantly to 1.50%±0.50% （P〈0.05） compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4 + CD25 + regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3 + CD4 + CD25 + regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased signifi- cantly to (459.2±76.9) U L -1 , total bilirubin increased to (124.1±33.7) μmol L -1 (P<0.05) and the ratio of Foxp3 + CD4 + CD25 + regulatory T cells decreased significantly to 1.50%±0.50% (P<0.05) compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

关 键 词：liver transplantation immune tolerance Foxp3＋ regulatory T cell GITR 

分 类 号：Q691.5[生物学—生物物理学] TQ464[化学工程—制药化工]