Release from regulatory T cell-mediated suppression during the onset of tissue-specific autoimmunity is associated with elevated IL-21
Release from regulatory T cell-mediated suppression during the onset of tissue-specific autoimmunity is associated with elevated IL-21
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DOI：
10.4049/jimmunol.180.8.5393
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发表时间：
2008-04-15
影响因子：
4.4
通讯作者：
Walker, Lucy S. K.
中科院分区：
文献类型：
--
作者：
Clough, Louise E.;Wang, Chun Jing;Walker, Lucy S. K.
调节性T细胞（Treg）的活性被广泛认为在预防针对自身抗原的病原性免疫反应中发挥着核心作用。然而，目前尚不清楚为什么这种调节在自身免疫发作期间被打破。我们研究了自发性糖尿病诱导过程中自身Ag特异性Treg。我们的数据揭示了疾病发作期间胰腺引流淋巴结中调节性和致病性胰岛反应性T细胞之间的平衡发生了变化。Treg功能在疾病开始期间没有受损，而是常规T细胞显示出对Treg介导的抑制的敏感性降低。从Treg抑制中释放与体内IL-21水平升高相关，并且提供这种细胞因子在体外和体内消除了Treg抑制。这些数据表明，Treg对外周组织的免疫保护可以被IL-21破坏，这表明了干预自身免疫的新策略。
The activity of regulatory T cells (Treg) is widely accepted to play a central role in preventing pathogenic immune responses against self-Ags. However, it is not clear why such regulation breaks down during the onset of autoimmunity. We have studied self-Ag-specific Treg during the induction of spontaneous diabetes. Our data reveal a shift in the balance between regulatory and pathogenic islet-reactive T cells in the pancreas-draining lymph nodes during disease onset. Treg function was not compromised during disease initiation, but instead conventional T cells showed reduced susceptibility to Treg-mediated suppression. Release from Treg suppression was associated with elevated levels of IL-21 in vivo, and provision of this cytokine abrogated Treg suppression in vitro and in vivo. These data suggest that immunological protection of a peripheral tissue by Treg can be subverted by IL-21, suggesting new strategies for intervention in autoimmunity.