类风湿性关节炎患者滑液中CD4^+CD25-FOXP3^+T细胞比例增加且抑制功能缺陷  

Increased percentage and defective inhibitory function of CD4^+CD25-FOXP3^+T cells in synovial fluid of patients with rheumatoid arthritis

作　　者：张睿 缪金林 张葵 郑朝晖 朱平 ZHANG Rui;MIAO Jinlin;ZHANG Kui;ZHENG Zhaohui;ZHU Ping(Department of Clinical Immunology,PLA Specialized Research Institute of Rheumatoid&Immunology,Xijing Hospital,Air Force Medical University,Xi'an 710032,China;Department of Clinical Immunology,National Translational Science Center for Molecular Medicine,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学西京医院临床免疫科,陕西西安710032 [2]空军军医大学国家分子医学转化中心,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2019年第11期961-966,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家重点研发计划(2017YFC0909002);国家自然科学基金(81801599)。

摘　　要：目的研究类风湿性关节炎(RA)患者外周血及关节滑液中CD4^+CD25-FOXP3^+T细胞[CD25-调节性T细胞(Treg)]数量及功能分子表达情况及其与疾病活动度之间的关系。方法收集RA患者60例及健康对照者69例,采用流式细胞术对RA患者外周血和滑液(33例)以及健康对照者外周血CD25-Treg比例及部分功能分子表达情况进行检测,并将相关数据与炎性指标及病情活动度进行相关性分析。采用Mann-WhitneyU检验、Spearman相关分析进行统计学分析。结果RA外周血中CD25-Treg占CD4+细胞比例较健康对照者外周血无明显差异,RA滑液中CD25-Treg比例较RA及健康对照者外周血均显著增高。将RA患者按疾病活动度及类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体、抗突变型瓜氨酸波形蛋白(MCV)抗体、抗角蛋白抗体(AKA)分组,RA外周血CD25-Treg比例在各组间比较无显著差异,并且与血沉(ESR)和C反应蛋白(CRP)水平无明显相关性。功能分子表达上,RA滑液CD25-Treg中CD39^+细胞比例显著低于健康对照者外周血,CD73^+细胞比例和转化生长因子β1阳性(TGF-β1^+)细胞比例显著低于RA患者及健康对照者外周血;细胞毒性T细胞相关蛋白4(CTLA4)和白细胞介素10(IL-10)表达水平在各组间均无明显差异。结论RA滑液中CD25-Treg比例增加,但CD25-Treg抑制功能分子CD39、CD73和TGF-β1表达下降,提示其抑制功能可能存在缺陷,进而导致局部炎症未得到有效控制。Objective To investigate the levels and function status of CD4^+CD25-FOXP3^+T cells(CD25-Tregs)in the peripheral blood and synovial fluid from rheumatoid arthritis(RA)patients,and their relationships with disease activity.Methods The study enrolled 60 RA patients and 69 healthy controls(HCs).Flow cytometry was used to analyze the percentage and phenotype of CD25-Tregs,and the results were analyzed by Mann-Whitey U test and Spearman correlation.Results The percentage of circulating CD25-Tregs in CD4+cells was compared between RA patients and HCs.However,the percentage of CD25-Tregs in RA synovial fluid was significantly higher than that in the peripheral blood of RA patients and HCs.When RA patients were grouped according to their disease activity or clinical indicators,such as rheumatoid factor(RF),anti-cyclic citrullinated peptides(CCP)antibody,anti-mutated citrullinated vimentin(MCV)antibody and anti-keratin antibody(AKA),circulating CD25-Tregs percentage was not significantly different among the groups,and had no correlation with the levels of erythrocyte sedimentation rate(ESR)and C reactive protein(CRP).The expression of CD39 in CD25-Tregs in RA synovial fluid was significantly lower than that in the peripheral blood of HCs.And CD73 and TGF-β1 expression in CD25-Tregs in RA synovial fluid were significantly lower than those in the peripheral blood of both RA patients and HCs.However,there was no significant difference in the expression of CTLA4 and IL-10 in CD25-Tregs among the groups.Conclusion The percentage of CD25-Tregs increases in RA synovial fluid.And the expression of CD39,CD73 and TGF-β1 decrease in CD25-Tregs,suggesting that its inhibitory function may be defective,resulting in local inflammation not being effectively controlled.

关 键 词：细胞毒性T细胞 疾病活动度 局部炎症 CD25 FOXP3 炎性指标 白细胞介素10 滑液 

分 类 号：R539.22[医药卫生—内科学] R392.12[医药卫生—临床医学]