title: Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model.
abstract: 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 significantly 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.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing 210009, China. zhangyewei@njmu.edu.cn
authors.forename: YeWei
authors.initials: Y
authors.lastname: Zhang
authors.forename: HeWei
authors.initials: H
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Bo
authors.forename: YinXue
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: JingFeng
authors.initials: J
authors.lastname: Sun
authors.forename: JianFei
authors.initials: J
authors.lastname: Wen
authors.forename: Xia
authors.initials: X
authors.lastname: He
authors.forename: GuoWen
authors.initials: G
authors.lastname: Yin
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood / Q000276:immunology; D000818:Animals; D001663:Bilirubin / Q000097:blood / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000097:blood / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology* / Q000528:radiation effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; D001663:Bilirubin