CD4^+CD25^+调节性T细胞在类风湿关节炎患者免疫耐受失衡中的变化

The Change of CD4^+CD25^+ Regulatory T Cells in Patients with Rheumatoid Arthritis

目的检测CD4+CD25+FoxP3+调节性T细胞(Treg)在类风湿关节炎(RA)患者外周血和关节液中的变化,探讨该细胞亚群在RA免疫耐受失衡中的作用。方法采用流式细胞术检测活动期RA患者关节液、外周血和健康对照外周血CD4+CD25+FoxP3+Treg细胞比例;实时定量聚合酶链反应(Real-time PCR)检测外周血和关节液单个核细胞FoxP3基因的表达。分析外周血CD4+CD25+FoxP3+Treg细胞比例与病情活动指标的相关性。结果活动期RA患者关节液CD4+CD25+FoxP3+Treg细胞比例(7.56%±2.89%)高于外周血(1.84%±0.97%)和健康对照外周血(2.19%±0.54%),差异均有统计学意义(P<0.01);RA患者抗环瓜氨酸肽(CCP)抗体(ACPA)阴性组外周血CD4+CD25+FoxP3+Treg细胞水平(2.85%±0.87%)高于ACPA阳性组(1.40%±0.63%,P<0.01)。活动期RA患者关节液单个核细胞FoxP3基因表达水平高于RA患者外周血和健康对照外周血(P<0.01);活动期RA患者外周血CD4+CD25+FoxP3+Treg细胞比例与疾病活动指标无相关性(P>0.05)。结论 RA患者关节液CD4+CD25+FoxP3+Treg细胞的变化更能反映RA炎症部位免疫耐受失衡机制。

Objective To investigate the change of CD4＋CD25＋FoxP3＋regulatory T cells（Treg）in peripheral blood（PB）and synovial fluid（SF）in patients with rheumatoid arthritis（RA）and its role in RA immune tolerance imbalance.Methods The frequency of CD4＋CD25＋FoxP3＋Treg in PB and SF cells in active RA patients and healthy volunteers were determined using flow cytometry.The expression of FoxP3 gene in mononuclear cells was analyzed by real-time PCR.The correlation between the frequency of CD4＋CD25＋FoxP3＋Treg in PB cells and disease activity indices was evaluated.Results ① Active RA patients had a higher level of CD4＋CD25＋FoxP3＋Treg in SF cells（7.56%±2.89%）than in PB cells（1.84%±0.97%）.Their level of CD4＋CD25＋FoxP3＋Treg in SF cells was also higher than that of healthy volunteers（2.19% ±0.54%）.Anti-CCP antibody（ACPA）positive RA patients had a lower level of CD4＋CD25＋FoxP3＋Treg（1.40%±0.63%）in PB cells compared with the ACPA negative RA patients（2.85%±0.87%）.② Active RA patients had a higher mRNA level of FoxP3in SF mononuclear cells than those inactive RA patients and healthy volunteers（P＆lt;0.01）.③ The frequency of CD4＋CD25＋FoxP3＋Treg in PB cells in active RA patients had no correlation with disease activity indices（P＆gt;0.05）.Conclusion Altered frequency of CD4＋CD25＋FoxP3＋Treg in SF cells of RA patients might contribute to RA immune tolerance imbalance in inflammatory joints.