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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Liu Y,Zhang P,Li J,Kulkarni AB,Perruche S,Chen W

doi

10.1038/ni.1607

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

632-40

issue

6

eissn

1529-2908

issn

1529-2916

pii

ni.1607

journal_volume

9

pub_type

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