Abstract
The molecular mechanisms directing the development of 'natural' CD4+CD25+Foxp3+ regulatory T cells (Treg cells) in the thymus are not thoroughly understood. We show here that conditional deletion of transforming growth factor-β receptor I (TβRI) in T cells blocked the appearance of CD4+CD25+Foxp3+ thymocytes at postnatal days 3–5. Paradoxically, however, beginning 1 week after birth, the same TβRI-mutant mice showed accelerated expansion of thymic CD4+CD25+Foxp3+ populations. This rapid recovery of Foxp3+ thymocytes was attributable mainly to overproduction of and heightened responsiveness to interleukin 2, as genetic ablation of interleukin 2 in TβRI-mutant mice resulted in a complete absence of CD4+CD25+Foxp3+ cells from the thymus and periphery. Thus, transforming growth factor-β signaling is critical to the thymic development of natural CD4+CD25+Foxp3+ Treg cells.
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Change history
04 May 2008
In the version of this article initially published online, error bars in Figures 2b, 3b,c, 4b–d, 5b, 7b and 8b were incorrect. The error has been corrected for all versions of the article.
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Acknowledgements
We thank S.M. Wahl and E.M. Shevach for critically reading the manuscript; S. Karlsson (Lund University) for Tgfbr1f/f mice; and U.H. von Andrian for discussions about the anti-CD49d experiments. Supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research of the National Institutes of Health.
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Y.L. designed and did experiments, analyzed data and contributed to the writing of the manuscript; P.Z. designed and did experiments; S.P. and J.L. did experiments; A.B.K. provided critical materials and helped analyze data; and W.C. initiated and directed the research, designed experiments, analyzed data and wrote the manuscript.
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Liu, Y., Zhang, P., Li, J. et al. A critical function for TGF-β signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat Immunol 9, 632–640 (2008). https://doi.org/10.1038/ni.1607
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DOI: https://doi.org/10.1038/ni.1607
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