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.
IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus
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Saskia Hemmers, Michail Schizas, Elham Azizi, Stanislav Dikiy, Yi Zhong, Yongqiang Feng, Grégoire Altan-Bonnet, Alexander Y. Rudensky; IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus. J Exp Med 4 November 2019; 216 (11): 2466–2478. doi: https://doi.org/10.1084/jem.20190993
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