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

Overview

abstract

  • 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.

publication date

  • August 21, 2019

Research

keywords

  • Interleukin-2
  • T-Lymphocytes, Regulatory
  • Thymocytes
  • Thymus Gland

Identity

PubMed Central ID

  • PMC6829602

Scopus Document Identifier

  • 85074553191

Digital Object Identifier (DOI)

  • 10.1186/gb-2008-9-9-r137

PubMed ID

  • 31434685

Additional Document Info

volume

  • 216

issue

  • 11