A function for interleukin 2 in Foxp3-expressing regulatory T cells.
Nat Immunol, 2005/11;6(11):1142-51.
Fontenot JD[1], Rasmussen JP, Gavin MA, Rudensky AY
Affiliations
PMID: 16227984
Impact factor: 31.25
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.
MeSH terms
Animals; Cell Differentiation; DNA-Binding Proteins; Forkhead Transcription Factors; Gene Expression Regulation; Green Fluorescent Proteins; Homeostasis; Immune Tolerance; Interleukin-2; Lymphocyte Activation; Mice; Mutation; Receptors, Interleukin-2; Signal Transduction; T-Lymphocytes
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