Blockade of LIGHT/LTbeta and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease.

Tamada Koji; Tamura Hideto; Flies DallasFu YangXinCelis EstebanPease LarryRBlazar BruceRChen Lieping

首页> 外文期刊>The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation >Blockade of LIGHT/LTbeta and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease.

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Blockade of LIGHT/LTbeta and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease.

机译：Blockade of LIGHT/LTbeta and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease.

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摘要

Previous studies have shown that blockade of LIGHT, a T cell costimulatory molecule belonging to the TNF superfamily, by soluble lymphotoxin beta receptor-Ig (LTbetaR-Ig) inhibits the cytotoxic T lymphocyte (CTL) response to host antigenic disparities and ameliorates lethal graft-versus-host disease (GVHD) in a B6 to BDF1 mouse model. Here, we demonstrate that infusion of an mAb against CD40 ligand (CD40L) further increases the efficacy of LTbetaR-Ig, leading to complete prevention of GVHD. We further demonstrate that alloantigen-specific CTLs become anergic upon rapid expansion, and persist in the tolerized mice as a result of costimulatory blockade. Transfer of anergic CTLs to secondary F1 mice fails to induce GVHD despite the fact that anergic CTLs can be stimulated to proliferate in vitro by antigens and cytokines. Our study provides a potential new approach for the prevention of lethal GVHD.

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《The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation》 |2002年第4期|549-557|共9页
作者
Tamada Koji; Tamura Hideto; Flies DallasFu YangXinCelis EstebanPease LarryRBlazar BruceRChen Lieping;
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作者单位

Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.;

ed.umsmed.edu;

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原文格式 PDF
正文语种英语
中图分类临床医学;
关键词
CD40 Ligand immunology; Graft vs Host Disease; Lymphotoxin; Membrane Proteins; 移植物抗宿主病; 淋巴毒素; 膜蛋白质类; T淋巴细胞; 肿瘤坏死因子;

Blockade of LIGHT/LTbeta and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease.

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