由同局部的效应细胞和调节性T细胞强制执行的免疫平衡
Zhiduo Liu1, Michael Y Gerner1, Nicholas Van Panhuys1
1Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.
Nature
|November 26, 2015
概括
调节性T细胞 (Treg细胞) 与自我抗原激活的T细胞聚集在一起,形成一个反循环. 这种Treg细胞活动通过限制T细胞反应来抑制自身免疫力并维持免疫平衡.
科学领域:
- 免疫学
- 细胞生物学
- 自体免疫性
背景情况:
- 调节FOXP3 (Treg细胞) 对于预防自身免疫至关重要.
- 在完整的组织中,Treg细胞的精确细胞机制和体内功能尚未完全理解.
- 目前尚不清楚Treg细胞是否能阻止自身特异性的T细胞激活或减轻已经激活的细胞的损伤.
研究的目的:
- 调查Treg细胞在预防自身免疫中的细胞事件和局部化.
- 确定Treg细胞对二次淋巴细胞组织内自我抗原激活的T细胞的反应作用.
- 阐明Treg细胞用于维持免疫平衡的反机制.
主要方法:
- 在小鼠模型中进行多重,定量成像.
- 对IL-2反应的Treg细胞聚类和STAT5酸化的分析.
- 在Treg细胞中诱导T细胞受体表达.
主要成果:
- 高抑制性Treg细胞表达化STAT5,与罕见的IL-2阳性,自我抗原激活的T细胞形成离散.
- 在Treg细胞中,局部IL-2诱导STAT5酸化构成了限制自身免疫反应的反回路.
- 干扰Treg细胞T细胞受体表达损害了聚类和调控能力,导致无控制的效应T细胞反应.
结论:
- 自主反应的T细胞经常被激活,产生细胞因子.
- 通过负反来抑制开始的自身免疫.
- 对于维持免疫平衡和预防自身免疫性疾病而言,Treg细胞聚类和T细胞受体信号传递至关重要.
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