Science China Life Sciences

, Volume 55, Issue 9, pp 774–781

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

  • YeWei Zhang
  • HeWei Zhao
  • Lin Bo
  • YinXue Yang
  • Xiang Lu
  • JingFeng Sun
  • JianFei Wen
  • Xia He
  • GuoWen Yin
Open AccessResearch Paper

DOI: 10.1007/s11427-012-4370-3

Cite this article as:
Zhang, Y., Zhao, H., Bo, L. et al. Sci. China Life Sci. (2012) 55: 774. doi:10.1007/s11427-012-4370-3

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.

Keywords

liver transplantationimmune toleranceFoxp3+regulatory T cellGITR
Download to read the full article text

Copyright information

© The Author(s) 2012

Authors and Affiliations

  • YeWei Zhang
    • 1
  • HeWei Zhao
    • 1
  • Lin Bo
    • 2
  • YinXue Yang
    • 3
  • Xiang Lu
    • 4
  • JingFeng Sun
    • 1
  • JianFei Wen
    • 1
  • Xia He
    • 5
  • GuoWen Yin
    • 6
  1. 1.Department of Hepatobiliary and Pancreatic SurgeryAffiliated Jiangsu Cancer Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of Rheumatism and ImmunologyAffiliated No. 2 Hospital of Suzhou UniversitySuzhouChina
  3. 3.Department of General SurgeryAffiliated Hospital of Ningxia Medical UniversityYinchuanChina
  4. 4.Department of GeriatricsThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  5. 5.Department of RadiotherapyAffiliated Jiangsu Cancer Hospital of Nanjing Medical UniversityNanjingChina
  6. 6.Department of InterventionalAffiliated Jiangsu Cancer Hospital of Nanjing Medical UniversityNanjingChina