Ⅰ型干扰素参与调节SLE外周T细胞活化和TLR表达谱的研究  

Involvement of typeⅠinterferon in modulating activation and TLRs expression on T cells in systemic lupus erythematosus

作　　者：梅瑞安 王树军[1] 刘芝翠[1] 李金枝[1] 张勇[1] 王佳琦[1] 沈浩[1] 潘萌[2] 王颖[1,3] 

机构地区：[1]上海交通大学医学院,上海市免疫学研究所,上海200025 [2]上海交通大学医学院附属瑞金医院,上海200025 [3]上海人类基因组研究中心,上海市疾病与健康基因组重点实验室,上海201203

出　　处：《现代免疫学》2012年第5期353-358,共6页Current Immunology

基　　金：国家自然科学基金面上项目(31170828);上海市国际科技合作基金项目资助(10410701600);上海市科委基金资助项目(102R1426200);上海市教委重点学科(J50207)

摘　　要：血清高水平Ⅰ型干扰素(typeⅠinterferon)是系统性红斑狼疮(SLE)患者重要的病理特征之一,外周高水平IFN-α对T细胞的免疫调节作用值得深入探讨。本研究首先比较分析了SLE患者外周血T细胞活化和TLR分子表达格局,结果显示SLE患者外周血CD4^+或CD8^+T细胞和正常人相比呈现出更加活化的表型变化,其表面活化标志CD69和HLA-DR表达阳性率均高于正常人;分析T细胞表达TLR分子格局发现,SLE患者较正常人T细胞中TLR分子的表达有明显升高,其中CD4^+T细胞中TLR8和TLR9的升高明显,而在CD8^+T细胞中明显升高的TLR分子有TLR3和TLR8;结合SLE病理状态下外周高水平IFN-α的持续存在,我们进一步分析了IFN-α对正常T细胞活化和TLR分子表达谱的影响,结果显示IFN-α协同TCR信号可以促进T细胞的活化,并上调T细胞中部分TLR分子的表达,其中CD4^+和CD8^+T细胞中TLR8的表达均明显上升。综合分析SLE患者和经IFN-α活化的正常T细胞的活化和TLR分子表达谱的变化格局,提示SLE病理状态下高水平的Ⅰ型干扰素可以与T细胞的持续活化有关,其对T细胞表达TLR分子格局的影响,特别是与核酸类分子配体相关的TLR分子的表达增高为内源性核酸类配体参与T细胞的活化提供了分子基础。High level type I interferon in serum is one of the key pathological properties of system lupus erythematosus （SLE）. In the present study, we intended to dissect its mechanisms on modulating the functionality of T cells under SLE path ogenesis. Through comparing the expression frequency of CD69 and HLA DR on the surface of T cells from either active SLE patients or healthy donors, we found that both CD4＋ and CD8＋ T cells exhibited much more activated populations. TLRs pro file were further analyzed in purified CD4 and CD8 T cells by real timePCR. Along with the increased activation of T cells, the expression levels of TLRs under investigation were also elevated. Among them, TLR8 and TLR9 were significantly upregula ted in CD4＋ T cells while TLR3 and TLR8 in CD8＋ T cells. More importantly, with the costimulation of antiCD3 antibody and interferonalpha, there exhibited the activation of T cells as well as the enhancement of TLRs expression in CD4 and CD8 T cells with similar TLRs profile observed in T cells from SLE patients. Our results indicated that there existed increased TLRs expression patterns in T cells under SLE pathogenesis which might be triggered and maintained by sustained high level type I interferon in the periphery. This might in turn facilitate the activation of T cell initiated by ligation of pathological endogenous ligands. These findings thus provide the novel mechanisms how IFN a modulate T cell functionality during the pathogenesis of SLE.

关 键 词：系统性红斑狼疮 T细胞 Ⅰ型干扰素 TOLL样受体 

分 类 号：R392.12[医药卫生—免疫学]