Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition

Nat Immunol. 2015 Jun;16(6):635-41. doi: 10.1038/ni.3171. Epub 2015 May 4.

Abstract

The thymic production of regulatory T cells (Treg cells) requires interleukin 2 (IL-2) and agonist T cell antigen receptor (TCR) ligands and is controlled by competition for a limited developmental niche, but the thymic sources of IL-2 and the factors that limit access to the niche are poorly understood. Here we found that IL-2 produced by antigen-bearing dendritic cells (DCs) had a key role in Treg cell development and that existing Treg cells limited new development of Treg cells by competing for IL-2. Our data suggest that antigen-presenting cells (APCs) that can provide both IL-2 and a TCR ligand constitute the thymic niche and that competition by existing Treg cells for a limited supply of IL-2 provides negative feedback for new production of Treg cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens / immunology
  • Cell Differentiation
  • Cell Line
  • Cellular Microenvironment
  • Dendritic Cells / physiology*
  • Feedback, Physiological
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / agonists*
  • T-Lymphocytes, Regulatory / physiology*
  • Thymus Gland / immunology*

Substances

  • Antigens
  • Interleukin-2
  • Receptors, Antigen, T-Cell