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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hemmers, S; Schizas, M; Azizi, E; Dikiy, S; Zhong, Y; Feng, Y; Altan-Bonnet, G; Rudensky, AY

Published Date

  • November 4, 2019

Published In

Volume / Issue

  • 216 / 11

Start / End Page

  • 2466 - 2478

PubMed ID

  • 31434685

Pubmed Central ID

  • PMC6829602

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20190993

Language

  • eng

Conference Location

  • United States