中华医学杂志（英文版）2010，Vol.123Issue(2)：212-215,4.DOI:10.3760/cma.j.issn.0366-6999.2010.02.017
Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver transplantation
Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver transplantation
QIN Lei 1GUAN Hong-geng 1ZHOU Xiao-jun 1YIN Jun 1LAN Jing 1QIAN Hai-xin1
作者信息
- 1. Department of General Surgery, the First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, China
- 折叠
摘要
Abstract
Background Blocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1 BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation. Methods The orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)- γ in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope. Results Isotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1 BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-γ. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially.Conclusions These results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.关键词
liver/transplantation1rat14-1BB/ligand1acute/rejectionKey words
liver/transplantation1rat14-1BB/ligand1acute/rejection引用本文复制引用
QIN Lei,GUAN Hong-geng,ZHOU Xiao-jun,YIN Jun,LAN Jing ,QIAN Hai-xin..Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver transplantation[J].中华医学杂志（英文版）,2010,123(2):212-215,4.
