A function for interleukin 2 in Foxp3-expressing regulatory T cells.
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.
Fontenot
Jason D
JD
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle, Washington 98195, USA. jfontenot@rockefeller.edu
Rasmussen
Jeffrey P
JP
Gavin
Marc A
MA
Rudensky
Alexander Y
AY
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D049452:Green Fluorescent Proteins