An essential role for the IL-2 receptor in T reg cell function

Nat Immunol. 2016 Nov;17(11):1322-1333. doi: 10.1038/ni.3540. Epub 2016 Sep 5.

Abstract

Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+ T cells but was important for limiting the activation of CD8+ T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of Treg cells separable from signaling via the T cell antigen receptor.

MeSH terms

  • Animals
  • Biomarkers
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Female
  • Immunomodulation
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • Receptors, Interleukin-2 / metabolism*
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Biomarkers
  • Cytokines
  • Receptors, Interleukin-2
  • STAT5 Transcription Factor