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A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.

Abstract : The molecular mechanisms directing the development of 'natural' CD4+CD25+Foxp3+ regulatory T cells (T(reg) cells) in the thymus are not thoroughly understood. We show here that conditional deletion of transforming growth factor-beta receptor I (TbetaRI) 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 TbetaRI-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 TbetaRI-mutant mice resulted in a complete absence of CD4+CD25+Foxp3+ cells from the thymus and periphery. Thus, transforming growth factor-beta signaling is critical to the thymic development of natural CD4+CD25+Foxp3+ T(reg) cells.
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https://www.hal.inserm.fr/inserm-00484154
Contributor : Philippe Saas <>
Submitted on : Tuesday, May 18, 2010 - 7:57:39 AM
Last modification on : Wednesday, September 16, 2020 - 10:43:29 AM

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Yongzhong Liu, Pin Zhang, Jun Li, Ashok Kulkarni, Sylvain Perruche, et al.. A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.. Nature Immunology, Nature Publishing Group, 2008, 9 (6), pp.632-40. ⟨10.1038/ni.1607⟩. ⟨inserm-00484154⟩

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