类风湿关节炎患者Th17细胞与调节性T细胞失衡的研究

目的观察类风湿性关节炎（RA）患者外周血Th17细胞与CD4^＋CD25^＋FoxP3^＋调节性T细胞（Treg）平衡状态与疾病的关系，分析Th17／Treg细胞免疫失衡在RA发病机制中的作用。方法采用流式细胞仪四色荧光抗体标记法分别对47例RA患者和39名健康志愿者（HVs）进行CD3、CD8、IL-17与CD4、CD25、F0xP3标记，测定Th17与调节性T细胞的比例变化及相关细胞因子IL-6、IL-23和IL-17水平。结果RA组患者外周血中，CD3^＋CD8^＋IL-17^＋T细胞占CD3^＋T淋巴细胞的百分比为（1．12±0．38）％，明显高于对照组（0．68±0．29）％（t=1．83，P〈0．05）；CD4’CD25’FoxP3^＋细胞占CD4^＋T淋巴细胞的百分比为（2．74±0．71）％，明显低于对照组（4．69±1．23）％（t=-2．94，P〈0．05）。相关细胞因子测定结果：IL-6水平在RA组为（13．5±3．7）ng／L，正常人为（4．6±0．9）ng／L（t=6．24，P〈0．01）；IL-23水平在RA组为（71±19）ng／L，正常人为（25±6）ng／L（t=14．37，P〈0．01）；IL-17水平在RA组为（122±33）ng／L，正常人为（37±9）ng／L（t=19．01，P〈0．01）；RA患者血清IL-6、IL-23和IL-17水平均明显升高。结论RA患者外周血Th17与CD4^＋CD25^＋FoxP3^＋调节性T细胞数量的异常可能是RA发病的重要因素，IL-6和IL-23的升高是引起这些改变的可能原因。

Study on the imbalance of Th17 cells/CD4 + CD25 + FoxP3 + regulatory T cells in patients with rheumatoid arthritis

Objective To observe the relationship between balance of peripheral blood Th17 cells and CD4 + CD25 + FoxP3 + regulatory T(Treg) cells in patients with rheumatoid arthritis (RA), and to analyze the role of Th17/Treg cell imbalance in the pathogenesis of RA. Methods Four-color flurescence flow cytometry was used to detect the CD3,CD8,IL-17 and CD4,CD25, FoxP3 markers in the peripheral blood of 47 patients and 39 healthy volunteers(HVs) . The proportions of Th17 cells and CD4 + CD25 + FoxP3 + regulatory T cells were compared between the two groups. IL-6, IL-23 and IL-17 in sera of these subjects were tested by ELISA.Results The quantity of CD3 + CD8-IL-17 + cells in RA patients was significantly higher than those in normal control[(1. 12 ± 0. 38) % vs. (0.68 ± 0.29) %; t = 1.83, P ＜ 0.05)]and the proportions of CD4 + CD25 +FoxP3+ cells were significantly lower in RA group compared with HV group[(2.74 ±0.71)% vs. (4.69 ±1.23) %; t = - 2. 94, P ＜ 0.05]. Meanwhile , IL-6, IL-23 and IL-17 in sera of RA were (13.5 ± 3.7)ng/L, (71 ± 19) ng/L and (122 ± 33) ng/L respectively. These three cytokines in healthy controls were (4.6±0.9) ng/L (t =6.24, P＜0.01),(25 ±6) ng/L (t =14.37,P＜0.01), and (37±9) ng/L (t =19.01,P＜0. 01) respectively. IL-6,IL-23 and IL-17 increased significantly in RA patients as compared with healthy donors. Conclusion This study suggested that abnormality of Th17 and CD4 + CD25 + FoxP3 + Tregs might depend on the increased IL-6 and IL-23 and it may play a critical role in the incidence of RA.