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

中文关键词:  CD4⁺CD25⁺调节性T细胞 类风湿关节炎 FoxP3

英文关键词:CD4⁺CD25⁺ regulatory T cells Rheumatoid arthritis FoxP3

中文摘要:

      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。

英文摘要:

      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 FoxP3 in SF mononuclear cells than those inactive RA patients and healthy volunteers (P< 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>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．