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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。
Serum high level of type I interferon is one of the important pathological features in patients with systemic lupus erythematosus (SLE). The immunomodulatory effect of high level peripheral IFN-α on T cells deserves further investigation. This study first comparative analysis of peripheral blood TLE activation and TLR molecular expression patterns in patients with SLE, the results showed that CD4 + or CD8 + T cells in peripheral blood of SLE patients showed more active phenotypic changes than normal, the surface The positive rate of activation markers CD69 and HLA-DR were higher than that of normal people. Analyzing the pattern of TLR expression in T cells, it was found that the expression of TLR in T cells of SLE patients was significantly higher than that in normal T cells And TLR9 increased significantly, while TLR3 and TLR8 were significantly increased in CD8 ~ + T cells; in the presence of persistently high levels of peripheral IFN-α in the pathological state of SLE, we further analyzed the effect of IFN-α on normal T lymphocyte activation and TLR expression profiles. The results showed that IFN-α synergized with TCR signaling can promote the activation of T cells and upregulate the expression of some TLR molecules in T cells. Among them, TLR8 in CD4 ~ + and CD8 ~ + T cells Expression were significantly increased. Comprehensive analysis of SLE patients and IFN-α-activated normal T cell activation and TLR molecular expression pattern changes, suggesting that high levels of SLE pathological state of type I interferon and T cells may be sustained activation of its T cells The effect of TLR molecule pattern expression, especially the increase of TLR molecules related to nucleic acid molecule ligands, provides the molecular basis for the involvement of endogenous nucleic acid ligands in T cell activation.