Department of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
J Rheumatol. 2011 Nov;38(11):2445-51. doi: 10.3899/jrheum.110377. Epub 2011 Sep 15.
Regulatory T cells are characterized by expression of the transcription factor FoxP3 and are thought to be involved in the pathogenesis of autoimmune diseases. We determined the frequency and phenotypic characteristics of CD4+FoxP3+ T cells in the blood and synovial fluid (SF) of patients with inflammatory joint diseases.
SF from 10 patients with ankylosing spondylitis (AS), 20 patients with other spondyloarthritides or with peripheral arthritis (pSpA), and 12 patients with rheumatoid arthritis (RA), and peripheral blood (PB) from 22 patients with AS, 19 with pSpA, 15 with RA, and 12 healthy controls were stained for CD4, FoxP3, CD25, and CD127 and different effector cytokines and then analyzed by flow cytometry. Methylation pattern of the Treg-specific demethylated region (TSDR) was determined after bisulfite treatment by quantitative polymerase chain reaction.
In all groups of patients we observed higher frequencies of Foxp3+ cells/CD4+ T cells within SF compared to PB. The frequency of synovial Foxp3+ cells/CD4+ T cells was significantly higher in patients with pSpA (18.79% ± 6.41%) compared to patients with AS (9.69% ± 4.11%) and patients with RA (5.95% ± 2.21%). CD4+FoxP3+ T cells were CD25+ and CD127- and lacked effector cytokine production in any of the different patient groups. The majority of the CD4+CD25+CD127- T cells showed demethylation of the TSDR within the Foxp3 locus, confirming its regulatory phenotype.
Our data show accumulation of Foxp3+ T cells within inflamed joints. These Foxp3+ T cells are mainly of stable T regulatory phenotype. The high frequency of Foxp3+ T cells in pSpA might contribute to the spontaneous resolution and remitting course of arthritis in pSpA as compared to the more persistent joint inflammation in RA.
调节性 T 细胞的特征是转录因子 FoxP3 的表达，被认为与自身免疫性疾病的发病机制有关。我们确定了炎症性关节疾病患者血液和滑液（SF）中 CD4+FoxP3+T 细胞的频率和表型特征。
10 例强直性脊柱炎（AS）患者、20 例其他脊柱关节炎或周围关节炎（pSpA）患者和 12 例类风湿关节炎（RA）患者的 SF，以及 22 例 AS、19 例 pSpA、15 例 RA 和 12 例健康对照者的外周血（PB）均进行 CD4、FoxP3、CD25 和 CD127 染色和不同效应细胞因子，并通过流式细胞术进行分析。采用定量聚合酶链反应，在亚硫酸氢盐处理后测定 Treg 特异性去甲基化区（TSDR）的甲基化模式。
在所有患者组中，我们观察到 SF 中 Foxp3+细胞/CD4+T 细胞的频率高于 PB。与 AS（9.69%±4.11%）和 RA（5.95%±2.21%）患者相比，pSpA 患者（18.79%±6.41%）的滑膜 Foxp3+细胞/CD4+T 细胞频率显著更高。在任何不同的患者组中，CD4+FoxP3+T 细胞均为 CD25+和 CD127-，且缺乏效应细胞因子产生。大多数 CD4+CD25+CD127-T 细胞在 Foxp3 基因座内显示出 TSDR 的去甲基化，证实了其调节表型。
我们的数据显示 Foxp3+T 细胞在炎症关节内聚集。这些 Foxp3+T 细胞主要是稳定的 T 调节表型。与 RA 中更持续的关节炎症相比，pSpA 中 Foxp3+T 细胞的高频率可能导致 pSpA 中关节炎的自发缓解和缓解过程。
