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Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling

Nature Immunology volume 6, pages 1152–1159 (2005)Cite this article

Abstract

Interleukin 2 signaling is believed to be critically involved in several aspects of CD25+ CD4+ regulatory T cell biology, such as intrathymic development, peripheral survival and suppressive function. Here we have analyzed the effects of interleukin 2 or CD25 deficiency on agonist-driven thymic development and the peripheral homeostasis of an antigen-specific population of regulatory T cells positive for forkhead family transcription factor Foxp3 and have correlated our observations with polyclonal suppressor populations. We found that the differentiation, acquisition of functional capacity and formation of a sizeable pool of suppressor T cells in the thymus was independent of interleukin 2 signaling, but that interleukin 2 was essential for the survival of mature Foxp3+ regulatory T cells.

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Figure 1: Selection of Foxp3+CD25+ Treg cells in TCR-HA × pgk-HA mice.
Figure 2: Thymic phenotype and Foxp3 expression in Il2+/+ and Il2−/− TCR-HA × pgk-HA mice.
Figure 3: Cycling is similar for thymocytes progressing toward a naive or Treg phenotype and is not affected by the absence of IL-2.
Figure 4: IL-2 dependence of peripheral CD25+TCR-HA+ CD4 T cells.
Figure 5: Phenotype of Il2ra−/− TCR-HA × pgk-HA mice.
Figure 6: Competitive bone marrow reconstitution.
Figure 7: Frequency of Foxp3+ cells and cycling of CD25+ CD4 SP cells in non–TCR-transgenic IL-2+/+ and IL-2−/− mice.

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Acknowledgements

We thank H. von Boehmer (Dana Farber Cancer Institute, Boston, Massachusetts) for TCR-HA × pgk-HA mice and for discussions. Supported by Boehringer Ingelheim (Research Institute of Molecular Pathology), the Austrian National Science Fund (Sonderforschungsbereich F023 and Z58-B01) and the European Union (FP6 Integrated Project Eurothymaide).

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  1. Research Institute of Molecular Pathology, Vienna, 1030, Austria

    Louise M D'Cruz & Ludger Klein

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  1. Louise M D'Cruz
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Correspondence to Ludger Klein.

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Supplementary information

Supplementary Fig. 1

CD25+Foxp3+ Treg are greatly reduced in the periphery of IL-2 deficient mice. (PDF 483 kb)

Supplementary Fig. 2

Phenotype of lymph node cells in Il2ra−/− TCR-HA × pgk-HA mice. (PDF 742 kb)

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D'Cruz, L., Klein, L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol 6, 1152–1159 (2005). https://doi.org/10.1038/ni1264

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