Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation

被引：16

作者：

Chen, Yong ^{[1
]}

Liu, Haizhong ^{[1
]}

Liu, Zuojin ^{[1
]}

Liang, Shaoyong ^{[1
]}

Chen, Jie ^{[1
]}

Long, Feiwu ^{[1
]}

Peng, Yong ^{[1
]}

Yan, Luenan ^{[2
]}

Gong, Jianping ^{[1
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobliliary Surg, Chongqing, Peoples R China

[2] Sichuan Univ, W China Hosp, Liver Transplantat Ctr, Chengdu, Peoples R China

来源：

AMERICAN JOURNAL OF SURGERY | 2009年 / 198卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Acute rejection; Inducible costimulator; Live transplantation; RNA interference; T lymphocyte; CD8(+) T-CELLS; ICOS; RESPONSES; ARTERIOSCLEROSIS; ACTIVATION; TOLERANCE; RECEPTOR; INJURY; CD4(+);

D O I：

10.1016/j.amjsurg.2008.09.014

中图分类号：

R61 [外科手术学];

学科分类号：

100210 [外科学];

摘要：

BACKGROUND: The role of inducible costimulator (ICOS) in transplantation immunity remains unclear. METHODS: A Lewis-to-Brown-Norway (BN) rat liver transplant model was used to explore the effect of ICOS blockade by small interference RNA. Recipient survival rate, number of CD25/ICOS-positive cells, ICOS mRNA and protein levels, and interferon-gamma and tumor-necrosis factor-alpha levels were determined. RESULTS: Recipient survival was significantly prolonged in rats treated with RNA interference. On day 7 after transplantation, there was a diminished frequency of CD25/ICOS-positive cells and an increased frequency of apoptotic T cells. Furthermore, we found that ICOS blockade could inhibit mRNA and protein expression of ICOS, decrease plasma levels of interferon-gamma and tumor-necrosis factor-alpha, suppress cell infiltration into grafts, and promote tolerance in the interference group. CONCLUSIONS: Our data demonstrate that RNA interference is a potent tool to down-modulate ICOS expression and protect alloggrafts from acute rejection. (c) 2009 Elsevier Inc. All rights reserved.

引用

页码：244 / 249

页数：6

共 16 条

[1]

ICOS co-stimulatory receptor is essential for T-cell activation and function [J].