IL-2 prevents deletion of developing T-regulatory cells in the thymus

Cell Death Differ. 2017 Jun;24(6):1007-1016. doi: 10.1038/cdd.2017.38. Epub 2017 May 12.

Abstract

In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second.

MeSH terms

  • Animals
  • Apoptosis
  • Female
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation
  • Interleukin-2 / metabolism*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Signal Transduction*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / physiology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2