炎性关节炎患者调节性T细胞亚群的变化及其对TNF-α拮抗剂治疗的反应  

Altered frequencies of regulatory T cell subsets in inflammatory arthritis patients and its significance in TNF-α blockade therapy

作　　者：张立斌[1] 林丽[1] 叶玲英[1] 殷健[1] 徐沪济[1] 

机构地区：[1]第二军医大学附属长征医院风湿免疫科,上海200003

出　　处：《现代免疫学》2014年第6期459-465,共7页Current Immunology

基　　金：国家自然科学基金资助项目(81102263)

摘　　要：人外周血CD4+Foxp3+调节性T细胞(regulatory T cells,Treg)的表型和功能存在异质性。本文用Foxp3和CD45RO共同标记Treg,研究强直性脊柱炎(AS)和类风湿性关节炎(RA)患者外周血Treg亚群数量以及接受TNF-α拮抗剂治疗对其亚群的改变。分别采集未经治疗的21例活动性AS患者和27例活动性RA患者的外周血。两种疾病各有14名患者接受TNF-α拮抗剂治疗40周。应用流式细胞术检测外周血Treg细胞数量。在CD4+T细胞中,活动性AS和RA患者其表型为CD45RO+Foxp3hi的效应型Treg(AS与正常对照相比,P=0.020;RA与正常对照相比,P<0.001)和表型为CD45RO-Foxp3low的幼稚型Treg(AS与正常对照相比,P=0.009;RA与正常对照相比,P=0.001)细胞数量均显著下降。与正常对照相比,AS和RA患者的CD4+Foxp3+T细胞中非Treg亚群细胞(表型为CD45RO+Foxp3low)的比例显著增加(AS与正常对照相比,P=0.027;RA与正常对照相比,P<0.001)。TNF-α拮抗剂治疗后,AS患者外周血中效应型Treg(P=0.025)和幼稚型Treg(P=0.005)细胞数量均增加,RA患者中仅效应型Treg细胞数量增加(P=0.003)。因此,不仅分析CD4+Foxp3+T细胞总数,而且分析其中不同表型的亚群细胞数量更有助于明确炎性关节炎的发病机制。It has been shown that human CD4^＋Foxp3^＋T cells are phenotypically and functionally heterogeneous.This study was undertaken to determine the frequencies of Treg subsets based on the expression of Foxp3 and CD45RO in patients with ankylosing spondylitis（AS）and rheumatoid arthritis（RA）and the effects of TNF-αblockade therapy on the change of Treg cells.Twenty one untreated patients with active AS,27 untreated patients with active RA were recruited,of which 14 cases from both diseases received 40 weeks TNF-αblockade therapy.The frequencies of circulating Treg subsets were determined using flow cytometry analysis.The frequencies of effector Treg（CD45RO＋Foxp3hi）[AS（0.486±0.067）%vs.NC（0.728±0.074）%,P=0.020;RA（0.344±0.064）% vs.NC（0.728±0.074）%,P〈0.001]and nave Treg（CD45RO-Foxp3low）[AS（1.102±0.151）%vs.NC（2.183±0.332）%,P=0.009;RA（1.000±0.152）%vs.NC（2.183±0.332）%,P=0.001]cell subsets decreased dramatically in active AS and RA patients.Compared to normal controls,CD4^＋Foxp3^＋cells in AS and RA patients contained a higher proportion of non-Treg（CD45RO＋Foxp3low）[AS（56.21±2.35）% vs.NC（45.71±3.54）%,P=0.027;RA（65.70±3.21）% vs.NC（45.71±3.54）%,P〈0.001].TNF-αblockade therapy increased the frequencies of both effector Treg[Δ（＋0.37±0.15）%,P=0.025]and nave Treg cells[Δ（＋0.63±0.19）%,P=0.005]in AS patients.However,only the frequency of effector Treg was restored in RA patients[Δ（＋0.30±0.08）%,P=0.003].By analyzing the subsets within CD4^＋Foxp3^＋T cells rather than whole CD4^＋Foxp3^＋T cell population may help us to better understand the pathogenesis of inflammatory arthritis.

关 键 词：调节性T细胞 TNF-Α 类风湿性关节炎 强直性脊柱炎 

分 类 号：R392[医药卫生—免疫学]