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1型糖尿病中CD4⁺Foxp3⁺CD25(- /低)调节性T细胞亚群的扩展

Extension of the CD4⁺Foxp3⁺CD25(-/low) regulatory T-cell subpopulation in type 1 diabetes mellitus.

作者信息

Zóka András, Barna Gábor, Somogyi Anikó, Műzes Györgyi, Oláh Ágnes, Al-Aissa Zahra, Hadarits Orsolya, Kiss Katalin, Firneisz Gábor

机构信息

2nd Department of Medicine, Semmelweis University , Budapest , Hungary .

出版信息

Autoimmunity. 2015;48(5):289-97. doi: 10.3109/08916934.2014.992518. Epub 2014 Dec 19.

DOI:10.3109/08916934.2014.992518
PMID:25523632
Abstract

Regulatory T-cells (Treg) have a crucial role in limiting physiologic autoreactivity. Foxp3 is a master regulator transcription factor of Treg differentiation and active Treg cells express high levels of IL-2 receptor α-chain (CD25). The aim of our study was to assess the key markers of Treg cell function in type 1 diabetic (T1DM) and control subjects by flow cytometry. The proportion of CD25(-/low) cells among CD4(+)Foxp3(+) Treg cells was higher in T1DM patients that might suggest a shifted proportion of the incomplete/reserve and the fully active (CD4(+)Foxp3(+)CD25(+)) Treg cell subpopulations in T1DM, similarly to other Th1-mediated autoimmune diseases. In addition to the decreased expression of CD25 and CTLA-4 in T1DM patients, a positive correlation was observed between the CD25 expression on CD4(+) and the CTLA-4 expression in CD8(-) T-lymphocytes both in the T1DM and in the healthy control group. Our results suggest an impaired balance of CD25(+) and CD25(-/low) Treg cells in T1DM which might reflect a decreased late phase peripheral Treg activation even in patients with a mean disease duration of more than a decade.

摘要

调节性T细胞(Treg)在限制生理性自身反应性方面发挥着关键作用。Foxp3是Treg分化的主要调节转录因子,活化的Treg细胞表达高水平的白细胞介素-2受体α链(CD25)。我们研究的目的是通过流式细胞术评估1型糖尿病(T1DM)患者和对照受试者中Treg细胞功能的关键标志物。T1DM患者中CD4(+)Foxp3(+) Treg细胞中CD25(-/低)细胞的比例更高,这可能表明T1DM中不完全/储备型和完全活化型(CD4(+)Foxp3(+)CD25(+))Treg细胞亚群的比例发生了变化,类似于其他Th1介导的自身免疫性疾病。除了T1DM患者中CD25和CTLA-4表达降低外,在T1DM组和健康对照组中,CD4(+)细胞上的CD25表达与CD8(-) T淋巴细胞中的CTLA-4表达之间均观察到正相关。我们的结果表明,T1DM中CD25(+)和CD25(-/低) Treg细胞的平衡受损,这可能反映了即使在平均病程超过十年的患者中,晚期外周Treg活化也有所降低。

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