Regulatory T (T reg) cells, a specialized subset of CD4+ T cells, are essential to prevent fatal autoimmunity. Expression of the T reg lineage-defining transcription factor Foxp3, and therefore their differentiation in the thymus, is dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that the majority of IL-2-producing cells in the thymus are mature CD4 single-positive (CD4SP) thymocytes and that continuous IL-2 production sustained thymic T reg cell generation and control of systemic immune activation. Furthermore, single-cell RNA sequencing analysis of CD4 thymocyte subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, which also contain T reg precursor cells. Thus, our results suggest that the thymic T reg cell pool size is scaled by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes. This IL-2-dependent scaling of thymic T reg cell generation by overall self-reactivity of a mature post-selection thymic precursor pool may likely ensure adequate control of autoimmunity.

中文翻译：

---

自身反应性CD4胸腺细胞产生的IL-2可调节胸腺中调节性T细胞的生成。

调节性T（T reg）细胞是CD4 + T细胞的专门子集，对于防止致命的自身免疫至关重要。T reg谱系定义转录因子Foxp3的表达及其在胸腺中的分化取决于T细胞受体（TCR）和白介素2（IL-2）信号传导。在这里，我们报告在胸腺中大多数产生IL-2的细胞是成熟的CD4单阳性（CD4SP）胸腺细胞，连续的IL-2产生可维持胸腺T reg细胞的生成并控制系统性免疫激活。此外，对CD4胸腺细胞亚群的单细胞RNA测序分析表明，IL-2在自反应性CD4SP胸腺细胞中表达，后者也含有T reg前体细胞。因此，我们的结果表明，胸腺T reg细胞库的大小由关键的利基因子IL-2决定，由自反应性CD4SP胸腺细胞产生。通过选择后成熟的胸腺前体池的整体自反应性，这种IL-2依赖性的胸腺T reg细胞生成的比例可确保对自身免疫的充分控制。