CD4(+) CD25(+) Foxp3(+) T regulatory cells with limited TCR diversity in control of autoimmunity.
CD4(+) CD25(+) Foxp3(+) T regulatory cells with limited TCR diversity in control of autoimmunity.
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DOI：
10.4049/jimmunol.0902379
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Malek TR
中科院分区：
文献类型：
--
作者：
Adeegbe D;Matsutani T;Yang J;Altman NH;Malek TR
人们对Treg细胞的高TCR多样性对于自身耐受性的重要性知之甚少。为了解决这个问题，在转移到IL-2 R β-/-小鼠中后测量Treg细胞的TCR多样性，所述小鼠由于Treg细胞的产生失败而产生致死性自身免疫。在这里，我们表明，预转移的Treg细胞的高TCR多样性导致选择具有较低TCR多样性的治疗性Treg细胞，其防止自身免疫。具有较低多样性的预转移Treg细胞导致通过具有甚至更受限的TCR多样性的实质性外周重塑来选择Treg细胞，这也抑制了自身免疫症状。因此，在由于Treg细胞产生失败而导致免疫耐受性严重破坏的情况下，仅通过一部分Treg TCR库实现对自身免疫的控制，但疾病风险增加。这些数据支持一种模型，其中高Treg TCR多样性是确保建立和维持自身耐受性的机制。
The importance of high TCR diversity of Treg cells for self-tolerance is poorly understood. To address this issue, TCR diversity was measured for Treg cells after transfer into IL-2Rβ-/- mice, which develop lethal autoimmunity due to failed production of Treg cells. Here we show that high TCR diversity of pre-transferred Treg cells led to selection of therapeutic Treg cells with lower TCR diversity that prevented autoimmunity. Pre-transferred Treg cells with lower diversity led to selection of Treg cells through substantial peripheral reshaping with even more restricted TCR diversity that also suppressed autoimmune symptoms. Thus, in a setting of severe breakdown of immune tolerance due to failed production of Treg cells, control of autoimmunity is achieved by only a fraction of the Treg TCR repertoire, but risk for disease increased. These data support a model where high Treg TCR diversity is a mechanism to ensure establishing and maintaining self-tolerance.
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DOI：
10.1084/jem.20081359
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lathrop SK;Santacruz NA;Pham D;Luo J;Hsieh CS
通讯作者：
Hsieh CS
影响因子：
15.3
作者：
Bayer, AL;Yu, AX;Adeegbe, D;Malek, TR
通讯作者：
Malek, TR
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
32.4
作者：
Correia-Neves, M;Waltzinger, C;Benoist, C
通讯作者：
Benoist, C
基于TCR的谱系追踪：没有证据表明胰岛中天然自我抗原的常规T细胞转化为调节性T细胞。
影响因子：
15.3
作者：
Wong, Jamie;Mathis, Diane;Benoist, Christophe
通讯作者：
Benoist, Christophe