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Literature DB >> 18438410

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

Yongzhong Liu¹, Pin Zhang, Jun Li, Ashok B Kulkarni, Sylvain Perruche, Wanjun Chen.

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.

Entities: Gene Species

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Year: 2008 PMID： 18438410 DOI： 10.1038/ni.1607

Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606

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Cited

270 in total

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Journal: Proc Natl Acad Sci U S A Date: 2012-01-04 Impact factor: 11.205

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

1. T-cell tolerance: central and peripheral.

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