A Function for Interleukin 2 in Foxp3-expressing Regulatory T Cells

Nat Immunol. 2005 Nov;6(11):1142-51. doi: 10.1038/ni1263. Epub 2005 Oct 16.

Abstract

Regulatory T cells (T(reg) cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most T(reg) cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in T(reg) cell biology has remained controversial. To directly assess the effect of IL-2 signaling on T(reg) cell development and function, we analyzed mice containing the Foxp3(gfp) knock-in allele that were genetically deficient in either IL-2 (Il2(-/-)) or CD25 (Il2ra(-/-)). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of T(reg) cells. Unexpectedly, Il2(-/-) and Il2ra(-/-) T(reg) cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg(-/-) mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of T(reg) cells in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Forkhead Transcription Factors
  • Gene Expression Regulation*
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / metabolism
  • Homeostasis / genetics
  • Homeostasis / immunology
  • Immune Tolerance / genetics
  • Interleukin-2 / genetics
  • Interleukin-2 / physiology*
  • Lymphocyte Activation / genetics
  • Mice
  • Mutation
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / immunology
  • Signal Transduction*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2
  • Receptors, Interleukin-2
  • Green Fluorescent Proteins