A two-step process for thymic regulatory T cell development
A two-step process for thymic regulatory T cell development
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DOI：
10.1016/j.immuni.2007.11.021
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发表时间：
2008-01-01
期刊：
影响因子：
32.4
通讯作者：
Hsieh, Chyi-Song
中科院分区：
文献类型：
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作者：
Lio, Chan-Wang Joaquim;Hsieh, Chyi-Song
调节性T（Treg）细胞发挥显性耐受作用需要识别自身抗原。然而，自身反应性胸腺细胞分化为Treg细胞亚群的机制尚不清楚。为了解决这个问题，我们在Foxp3⁻CD4⁺CD8⁻胸腺细胞中寻找Treg细胞的直接前体细胞。通过胸腺内转移实验，我们发现CD25⁺⁺亚群中Treg细胞前体细胞高度富集。在TCR -β转基因模型中，通过对T细胞受体（TCR）库的分析来追踪胸腺细胞发育，这一结果得到了支持。这些Treg细胞前体细胞处于一个发育阶段，在这个阶段它们无需进一步的TCR参与即可表达Foxp3，仅需白细胞介素 - 2（IL - 2）或IL - 15的刺激。因此，我们提出自身反应性胸腺细胞分化为Treg细胞亚群是通过一种指导性而非随机选择性的模型发生的，即TCR信号导致近端IL - 2信号成分的表达，促进细胞因子介导的Foxp3诱导。
Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3(-)CD4(+)CD8(-) thymocytes. By using intrathymic transfer, we found that the CD25(hi) subset is highly enriched in Treg cell precursors. This was supported by tracking of thymocyte development via analysis of T cell receptor (TCR) repertoires in a TCR-beta transgenic model. These Treg cell precursors exist at a developmental stage where they are poised to express Foxp3 without further TCR engagement, requiring only stimulation by interleukin-2 (IL-2) or IL-15. Thus, we propose that the selection of self-reactive thymocytes into the Treg cell subset occurs via an instructive rather than stochastic-selective model whereby TCR signals result in the expression of proximal IL-2 signaling components facilitating cytokine-mediated induction of Foxp3.