Antigen-specific peripheral shaping of the natural regulatory T cell population.
Antigen-specific peripheral shaping of the natural regulatory T cell population.
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DOI：
10.1084/jem.20081359
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发表时间：
2008-12-22
期刊：
影响因子：
--
通讯作者：
Hsieh CS
中科院分区：
文献类型：
--
作者：
Lathrop SK;Santacruz NA;Pham D;Luo J;Hsieh CS
尽管调节性T(T Reg)细胞被认为主要在胸腺发育，但形成保护性T reg细胞群体的外周事件尚不清楚。我们分析了外周血中CD_4~+T细胞受体β链固定的小鼠的细胞表型和定位。我们发现，Treg(FOXP3+)细胞在解剖位置上表现出明显的TCR偏斜，其方式类似于抗原经验细胞(CD44hiFoxp3−)，但不是幼稚(CD44loFoxp3−)细胞，尽管CD44HI和T reg细胞使用的TCR大多不同。这可能与外周转换无关，我们估计这只会在成年人中产生一小部分外周T细胞。然而，在淋巴细胞减少的宿主中，在foxp3−细胞诱导的免疫反应中很容易观察到转化。有趣的是，转化后的Foxp3+和扩增后的Foxp3−TCR谱不同，提示Foxp3+细胞的产生不是Foxp3−T细胞抗原激活后的自动过程。这些TCR在原代单抗T细胞中的逆转录病毒表达证实了转换不需要事先的细胞条件。因此，这些数据表明，TCR的特异性在外周转化过程中起着至关重要的作用，并在塑造外周T细胞群以适应局部抗原环境方面发挥着关键作用。
Although regulatory T (T reg) cells are thought to develop primarily in the thymus, the peripheral events that shape the protective T reg cell population are unclear. We analyzed the peripheral CD4+ T cell receptor (TCR) repertoire by cellular phenotype and location in mice with a fixed TCRβ chain. We found that T reg (Foxp3+) cells showed a marked skewing of TCR usage by anatomical location in a manner similar to antigen-experienced (CD44hiFoxp3−) but not naive (CD44loFoxp3−) cells, even though CD44hi and T reg cells used mostly dissimilar TCRs. This was likely unrelated to peripheral conversion, which we estimate generates only a small percentage of peripheral T reg cells in adults. Conversion was readily observed, however, during the immune response induced by Foxp3− cells in lymphopenic hosts. Interestingly, the converted Foxp3+ and expanded Foxp3− TCR repertoires were different, suggesting that generation of Foxp3+ cells is not an automatic process upon antigen activation of Foxp3− T cells. Retroviral expression of these TCRs in primary monoclonal T cells confirmed that conversion did not require prior cellular conditioning. Thus, these data demonstrate that TCR specificity plays a crucial role in the process of peripheral conversion and in shaping the peripheral T reg cell population to the local antigenic landscape.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
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Rudensky, AY
影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
32.4
作者：
Correia-Neves, M;Waltzinger, C;Benoist, C
通讯作者：
Benoist, C
影响因子：
4.4
作者：
Cobbold, SP;Castejon, R;Waldmann, H
通讯作者：
Waldmann, H