BACKGROUND Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-β is a key regulator of Treg development and function. OBJECTIVE The objective of this study is to determine whether the expression of functionally relevant TGF-β-regulated molecules is altered in Tregs from patients with MS. METHODS Expression of nine Treg markers was analyzed by multi-color flow cytometry in CD4+ T cells and Treg subpopulations of 31 untreated MS patients and age- and sex-matched healthy donors (HDs). Correlations between Treg marker expression and clinical variables were sought. RESULTS Expression of the transcription factor Helios, which defines thymic-derived Tregs, was decreased in this Treg subpopulation. The frequency of peripherally generated Tregs was increased in patients with MS, particularly in patients with progressive MS. Low frequencies of thymic-derived Tregs were associated with magnetic resonance imaging (MRI) lesion-burden and a high relapse rate. Four surface markers associated with TGF-β signaling (ABCA1, BTLA, DNAM-1, and GARP) were differentially expressed on Tregs from patients with MS and HDs. Expression levels of CD73, CD103, ABCA1, and PAR2 showed strong correlations with disease severity. CONCLUSION We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.

中文翻译：

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鉴定与多发性硬化严重程度相关的调节性 T 细胞分子

背景调节性 CD4+ T 细胞 (Treg) 在多发性硬化症 (MS) 患者中表现出功能改变。转化生长因子 (TGF)-β 是 Treg 发育和功能的关键调节因子。目的 本研究的目的是确定 MS 患者 Treg 中功能相关的 TGF-β 调节分子的表达是否发生改变。方法 通过多色流式细胞术分析 31 名未经治疗的 MS 患者和年龄和性别匹配的健康供体 (HD) 的 CD4+ T 细胞和 Treg 亚群中 9 种 Treg 标记物的表达。寻求 Treg 标志物表达与临床变量之间的相关性。结果 在该 Treg 亚群中，定义胸腺衍生 Treg 的转录因子 Helios 的表达降低。MS 患者外周生成 Treg 的频率增加，尤其是进展性 MS 患者。胸腺源性 Treg 的低频与磁共振成像 (MRI) 病变负担和高复发率有关。与 TGF-β 信号传导相关的四种表面标志物（ABCA1、BTLA、DNAM-1 和 GARP）在 MS 和 HD 患者的 Treg 上差异表达。CD73、CD103、ABCA1 和 PAR2 的表达水平显示出与疾病严重程度的强相关性。结论 我们已经确定了 MS 患者 Treg 上异常表达的新标记，可以检测患有严重疾病的患者。与 TGF-β 信号传导相关的四种表面标志物（ABCA1、BTLA、DNAM-1 和 GARP）在 MS 和 HD 患者的 Treg 上差异表达。CD73、CD103、ABCA1 和 PAR2 的表达水平显示出与疾病严重程度的强相关性。结论 我们已经确定了 MS 患者 Treg 上异常表达的新标记，可以检测患有严重疾病的患者。与 TGF-β 信号传导相关的四种表面标志物（ABCA1、BTLA、DNAM-1 和 GARP）在 MS 和 HD 患者的 Treg 上差异表达。CD73、CD103、ABCA1 和 PAR2 的表达水平显示出与疾病严重程度的强相关性。结论 我们已经确定了 MS 患者 Treg 上异常表达的新标记，可以检测患有严重疾病的患者。