类风湿关节炎患者外周血Th0/Th1/Th2细胞亚群失衡的研究

目的研究类风湿关节炎(RA)患者外周血辅助性T细胞(T-helpercell,Th)亚群的状态,以探讨Th细胞亚群(Th0/Th1/Th2)在RA发病机制中的作用。方法利用流式细胞仪检测技术,采用三色标记法,在外周血单个细胞水平上同时进行细胞膜表面(CD4)和细胞内细胞因子白细胞介素(IL)-4、干扰素(IFN)-γ]的测定,检测33例活动期RA患者和16名正常对照者外周血中T细胞亚群(CD3+/CD4+/CD8+T细胞)及Th细胞亚群的比例;并分析早期RA组(病程≤2年,17例)与非早期RA组(病程>2年,16例),骨侵蚀组(19例)与无骨侵蚀组(14例),类风湿因子(RF)阳性组(23例)与RF阴性组(10例)Th细胞亚群的比例。结果①与正常对照组相比,RA组外周血CD3+CD4+T淋巴细胞升高(P<0.05);Th0、Th1细胞的比例降低(P<0.05);T细胞亚群、Th细胞亚群变化与RA疾病活动相关;②与非早期RA组相比,早期RATh1细胞、Th1/Th2比值升高,Th2降低(P<0.05),早期RA患者Th1细胞比例与血沉、C-反应蛋白、晨僵时间呈正相关;非早期RA患者Th2细胞比例与血沉、晨僵时间呈正相关;③与无骨侵蚀组比较,有骨侵蚀组Th1细胞、Th1/Th2明显降低,Th2细胞升高(P<0.05);④RF阳性组与阴性组间Th细胞亚群及Th1/Th2比值差异均无统计学意义。结论CD4+T细胞在RA的发病机制中起着重要的作用,RA外周血中存在着Th细胞亚群的不平衡,Th细胞失衡的模式在RA的病程中并不是固定的,早期RA外周血以Th1细胞为主,慢性RA则以Th2细胞相对占优势,并与疾病的活动性、骨侵蚀有密切关系。

The imbalance of T-helper cell subsets in peripheral blood of patients with rheumatoid arthritis

Objective To explore the important roles of T helper cell subsets(Th0/Th1/Th2)in the pathogenesis of rheumatoid arthritis(RA)by analyzing peripheral T-helper cell subsets in patients with RA.Methods The ratios of T cell subsets(CD3+/CD4+/CD8+ T cells)and T helper cell subsets(Th0/Th1/Th2)in peripheral blood from active RA(n=33)and healthy controls(n=16)were determined by detection of both membranous(CD4)and intracellular(IL-4,IFN-gamma)cytokines using three-color flow cytometry at single-cell level.Specifically,the ratios of T helper subsets were compared between early RA(persistence ≤ 2 years,n=17)and chronic RA(persistence > 2 years,n=16)groups,bone erosion(n=19)and non bone erosion(n=14)groups,RF-positive(n=23)and RF-negative(n=10)groups.Results CD4+ T cell and the ratio of CD4/CD8 was found significantly higher in peripheral blood of patients with RA than that in the healthy controls,and CD4+ T cell was correlated significantly with health assessment questionnaire(HAQ).The mean percentage of Th0 and Th1 cell was significantly decreased in patients with RA as compared with healthy individuals.Although no differences were found in Th2 subsets and the ratio of Th1/Th2 between the two groups,the percentage of Th2 was positively correlated with erythrocyte sedimentation rate(ESR),C reaction protein and morning stiffness time,and the ratio of Th1/Th2 was negatively correlated with ESR.There were no differences in CD4+ T cell and Th0 subsets between early RA and late RA,whereas the early RA patients were predominated in Th1 subsets and higher ratio of Th1/Th2,and late RA was predominated in Th2 subsets.In early RA,Th1 subsets were positively correlated with ESR,C-reactive protein(CRP)and the duration of morning stiffness;in late RA,Th2 subsets correlated positively with ESR and the duration of morning stiffness.The Th1 subsets and the ratio of Th1/Th2 were significantly decreased and Th2 subsets were significantly increased in bone-erosive RA as compared with non bone-erosive RA.There were no differences in Th0/Th1/Th2 subsets between RF positive and negative RA groups.Conclusion CD4+T contributes substantially to the development of RA.The imbalance of peripheral Th cell subsets was found in RA,but the pattern may vary with several RA groups.Th1 cells in early RA and Th2 in late RA were predominant subsets,and both showed close relationships with disease severity.