IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus

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.

Source: The Journal of Experimental Medicine - November 3, 2019 Category: Internal Medicine Authors: Hemmers, S., Schizas, M., Azizi, E., Dikiy, S., Zhong, Y., Feng, Y., Altan-Bonnet, G., Rudensky, A. Y. Tags: Autoimmunity, Tolerance Brief Definitive Reports Source Type: research