【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。更多还原

【Abstract】 High level typeⅠinterferon 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 pathogenesis. 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 profile were further analyzed in purified CD4 and CD8 T cells by real time-PCR.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 up-regulated in CD4~+ T cells while TLR3 and TLR8 in CD8~+ T cells.More importantly,with the costimulation of anti-CD3 antibody and interferon-alpha,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 typeⅠinterferon 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-αmodulate T cell functionality during the pathogenesis of SLE.更多还原