Rheumatoid arthritis (RA) is frequent systemic autoimmune disease characterized by excessive activation of collagen-specific T helper cells, and elevated level of autoantibodies in the serum. Development of RA is associated with defect in compartment of regulatory CD4+Foxp3+ T cells (Treg), but data concerning suppressive potential of Treg population in RA patients are contradictory and depend on the stage of disease. In this study we aimed to characterize abundance and phenotypic markers of CD4+Foxp3+ Treg in peripheral blood of healthy donors compared to untreated early RA patients to find potential correlations with the disease activity, antibody level, and absolute numbers and proportion of different subpopulations of T cells. Moreover, we assessed the influence of methotrexate (MT) treatment on percentage and absolute numbers of CD4+Foxp3+ Treg from the peripheral blood of untreated early RA patients. We demonstrate that increase and phenotypic changes in Treg population correlate well with response to MT. Analysis of the cohorts of matched RA patients (n = 45) and healthy controls (n = 20) revealed that patients with untreated early RA demonstrate substantial decrease in blood Treg percentage and absolute number, as well as low level of activated Treg surface markers in comparison to healthy control. The defect in Treg compartment negatively correlates with both RA activity and antibody level. MT treatment of patients with early untreated RA increases both proportion and absolute number of Treg with high level of activation markers, suggesting an increase of their functional capacity. Here we speculate the role of Tregs as specific cellular marker of successful RA treatment.

中文翻译：

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早期未治疗的类风湿关节炎患者的调节性T细胞：甲氨蝶呤治疗过程中的表型改变。

类风湿关节炎（RA）是一种常见的全身性自身免疫性疾病，其特征在于胶原特异性T辅助细胞的过度活化以及血清中自身抗体水平的升高。RA的发展与调节性CD4 + Foxp3 + T细胞（Treg）隔室的缺陷有关，但是有关RA患者中Treg抑制潜力的数据是相互矛盾的，并取决于疾病的阶段。在这项研究中，我们旨在表征健康供体外周血中CD4 + Foxp3 + Treg的丰度和表型标志物，与未经治疗的早期RA患者相比，发现其与疾病活动性，抗体水平以及T的不同亚群的绝对数量和比例的潜在相关性细胞。此外，我们评估了甲氨蝶呤（MT）治疗对未经治疗的早期RA患者外周血CD4 + Foxp3 + Treg的百分比和绝对数的影响。我们证明，Treg群体的增加和表型变化与对MT的反应密切相关。对匹配的RA患者（n = 45）和健康对照（n = 20）的队列分析显示，未经治疗的早期RA患者在血液中的Treg百分比和绝对值显着降低，并且激活的Treg表面标志物水平较低。与健康对照相比。Treg区室中的缺陷与RA活性和抗体水平均负相关。早期未接受RA的患者进行MT治疗会增加Treg的比例和绝对数量，并带有高水平的激活标记物，提示其功能增强。在这里我们推测Tregs作为成功的RA治疗的特定细胞标记物的作用。