Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes.
Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes.
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DOI：
10.4049/jimmunol.1003099
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Brusko TM
中科院分区：
文献类型：
--
作者：
McClymont SA;Putnam AL;Lee MR;Esensten JH;Liu W;Hulme MA;Hoffmüller U;Baron U;Olek S;Bluestone JA;Brusko TM
调节性T细胞(Tregs)因其在控制自身免疫中的重要作用而成为一个有吸引力的治疗靶点。然而，最近的动物研究为Treg间隔内的功能异质性和谱系可塑性提供了证据。为了更好地了解人类Treg细胞在1型糖尿病中的可塑性，我们鉴定了人类γ+CD127lo/−CD25+Treg细胞的干扰素-CD127lo亚群。采用表观遗传学方法检测1型糖尿病患者外周血中Treg特异性去甲基化区(TSDR)和干扰素-γ+细胞亚群的频率。对纯化的干扰素-γ+Treg细胞的抑制功能、TSDR去甲基化程度以及Treg谱系标志物FOXP3和Helios的表达进行评估。1型糖尿病患者外周血中Tregs的比例与健康对照组相比无显著差异，但FoxP3+干扰素-γ+细胞比例明显高于健康对照组。纯化的干扰素-γ+Treg表达FOXP3FOXP3并具有抑制活性，但缺乏Helios表达，并且主要在TSDR处甲基化，具有适应性Treg的特征。Naive Tregs能上调IL-12诱导的Th1相关T-bet、CXCR3和干扰素-γ的表达。值得注意的是，来自胸腺的天然Tregs也显示了Th1分化的能力，而不伴随Helios表达的丧失或TSDR去甲基化。
Regulatory T cells (Tregs) constitute an attractive therapeutic target given their essential role in controlling autoimmunity. However, recent animal studies provide evidence for functional heterogeneity and lineage plasticity within the Treg compartment. To understand better the plasticity of human Tregs in the context of type 1 diabetes, we characterized an IFN-γ–competent subset of human CD4+CD127lo/−CD25+ Tregs. We measured the frequency of Tregs in the peripheral blood of patients with type 1 diabetes by epigenetic analysis of the Treg-specific demethylated region (TSDR) and the frequency of the IFN-γ+ subset by flow cytometry. Purified IFN-γ+ Tregs were assessed for suppressive function, degree of TSDR demethylation, and expression of Treg lineage markers FOXP3 and Helios. The frequency of Tregs in peripheral blood was comparable but the FOXP3+IFN-γ+ fraction was significantly increased in patients with type 1 diabetes compared to healthy controls. Purified IFN-γ+ Tregs expressed FOXP3 and possessed suppressive activity but lacked Helios expression and were predominately methylated at the TSDR, characteristics of an adaptive Treg. Naive Tregs were capable of upregulating expression of Th1-associated T-bet, CXCR3, and IFN-γ in response to IL-12. Notably, naive, thymic-derived natural Tregs also demonstrated the capacity for Th1 differentiation without concomitant loss of Helios expression or TSDR demethylation.
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影响因子：
2.6
作者：
Brusko, Todd;Atkinson, Mark
通讯作者：
Atkinson, Mark
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Hoffmann, Petra;Boeld, Tina J.;Edinger, Matthias
通讯作者：
Edinger, Matthias
影响因子：
15.3
作者：
Bonecchi, R;Bianchi, G;Bordignon, P P;D'Ambrosio, D;Lang, R;Borsatti, A;Sozzani, S;Allavena, P;Gray, P A;Mantovani, A;Sinigaglia, F
通讯作者：
Sinigaglia, F
DOI：
10.1073/pnas.0509484103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Gavin, MA;Torgerson, TR;Rudensky, AY
通讯作者：
Rudensky, AY