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A function for interleukin 2 in Foxp3-expressing regulatory T cells

Nature Immunology volume 6, pages 1142–1151 (2005)Cite this article

An Erratum to this article was published on 01 April 2006

This article has been updated

Abstract

Regulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor α-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp 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 Treg cells. Unexpectedly, Il2−/− and Il2ra−/− Treg 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 Treg cells in vivo.

*Note: In the version of this article initially published, the GEO database accession number is missing. This should be the final subsection of Methods, as follows:  Accession code. GEO: microarray data, GSE4179. The error has been corrected in the PDF version of the article.

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Figure 1: Foxp3-expressing T cells develop in the absence of IL-2 signaling.
Figure 2: Activated phenotype of Foxp3-expressing T cells in the absence of IL-2 signaling.
Figure 3: CD25-deficient Treg cells are not competitive in the periphery.
Figure 4: IL-2 is dispensable for the Treg cell suppressive function.
Figure 5: IL-2 signaling potentiates CD25 and Foxp3 expression in Treg cells.
Figure 6: Gene expression analysis of the effects of IL-2 signaling on Treg cells.
Figure 7: Signal derived from the common γ-chain is required for Foxp3 expression.

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Change history

  • 10 March 2006

    In the version of this article initially published, the GEO database accession number is missing. This should be the final subsection of Methods, as follows: Accession code. GEO: microarray data, GSE4179.The error has been corrected in the PDF version of the article.

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Acknowledgements

We thank all members of the Rudensky lab for advice and discussions; and K. Forbush, L. Hsing, Y. Liang and L. Karpik for technical expertise and mouse colony management. Supported by National Institutes of Health (R01AI034206 to A.Y.R.) and Howard Hughes Medical Institute (A.Y.R.).

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Author notes

  1. Jason D Fontenot

    Present address: Laboratory of Lymphocyte Signaling, Rockefeller University, New York, New York, 10021, USA

Authors and Affiliations

  1. Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, 98195, Washington, USA

    Jason D Fontenot, Jeffrey P Rasmussen, Marc A Gavin & Alexander Y Rudensky

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  1. Jason D Fontenot
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Correspondence to Jason D Fontenot or Alexander Y Rudensky.

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Supplementary information

Supplementary Fig. 1

Il2−/− and Il2ra−/− mice develop a less severe lymphoproliferative autoimmune syndrome than Foxp3− mice. (PDF 485 kb)

Supplementary Fig. 2

IL-2 neutralization reduces the percentage of Foxp3+ Treg cells and reduces amounts of CD25 and Foxp3 in Foxp3+ Treg cells. (PDF 623 kb)

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Fontenot, J., Rasmussen, J., Gavin, M. et al. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6, 1142–1151 (2005). https://doi.org/10.1038/ni1263

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