地塞米松对系统性红斑狼疮患者外周血T细胞亚群的影响

Effect of dexamethasone on T cell subsets in peripheral blood of patients with systemic lupus erythematosus

研究地塞米松对系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中Th17、Tc17、Th1、Tc1等T细胞亚群表达的影响。收集30例确诊的SLE患者和22例健康志愿者作为对照组。SLE患者和正常对照者的PBMC分空白孔、佛波酯(PMA)/离子霉素(Ionomycin)孔、PMA/Ionomycin+地塞米松(DEX)孔行体外培养,运用四色流式细胞术检测PBMC表达Th17、Tc17、Th1、Tc1、IL-17/IFN-γ双阳细胞等T细胞亚群的百分比。未经刺激的状态下,SLE患者PBMC中各群T细胞的百分比较正常人无差异;经PMA刺激后,SLE患者外周血Th17、Tc1、CD3+CD8-IL-17+IFN-γ+细胞的比例显著高于对照组,SLE患者Th1、Tc17细胞百分比与对照组相比,差异无统计学意义(P>0.05);地塞米松能明显抑制活化状态下的PBMC中表达Th17、Tc17、Th1、Tc1细胞的比例(P<0.05),还可降低SLE患者PBMC培养中CD4+T细胞表达IL-17、IFN-γ的平均荧光强度。SLE患者体内T细胞亚群的表达水平存在明显异常,地塞米松能干扰SLE患者体内细胞因子网络失衡的免疫病理过程,且对表达IL-17、IFN-γ的T细胞均有明显的抑制作用,为临床使用糖皮质激素治疗SLE提供新的理论依据和实验室基础。

To investigate the effect of dexamethasone（DEX） on the expressions of T cell subsets Th17、Tc17、Th1、Tc1 cells in the peripheral blood mononuclear cells（PBMCs） of patients with systemic lupus erythematosus（SLE）,30 hospitalized SLE patients and 22 healthy volunteers served as normal control were recruited and their PBMCs were separated.Then,the PBMCs both of patients and controls were cultivated in vitro in medium with phorbol myristate acetate（PMA）/ionomycin or PMA/ionomycin＋dexamethasone for 6 hours.The percentages of Th17、Tc17、Th1、Tc1 and IL-17/IFN-γ double-positive cells in PBMCs were assayed by means of 4-color ommun of louorescent staining and flow cytometry.It was found that no significant differences in the percentages of various T cell subsets between patients and controls was demonstrated under un-stimulated condition.However,after stimulation with PMA,the proportions of Th17、Tc17、Th1、Tc1、CD3＋CD8-IL-17＋IFN-γ＋、CD3＋CD8＋IL-17＋IFN-γ＋ cells in PBMCs of patients were significantly higher than those of controls,but no statistic differences was found between patients and normal controls in the percentages of Th1 and Tc17 cells（P0.05）.In addition,DEX could significantly decrease the percentages of Th17、Tc17、Th1、Tc1 cells in PBMCs under active status（P0.05）and also reduce the mean fluorescent intension（MFI） of IL-17 and IFN-γ in CD4＋T cells of PBMCs of patients.From these observations it is obvious that abnormal expression of T subset cells exists in the PBMCs of SLE patients,in which DEX interferes the immuno-pathological process in cytokine network imbalance of SLE patients and inhibits the production of T cells expressing IL-17 or IFN-γ.Our result may provide some laboratory proof and reference for the clinical use of corticosteroids.