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

被引：448

作者：

Liu, Yongzhong ^{[1
]}

Zhang, Pin ^{[1
]}

Li, Jun ^{[1
]}

Kulkarni, Ashok B. ^{[2
]}

Perruche, Sylvain ^{[1
]}

Chen, WanJun ^{[1
]}

机构：

[1] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA

[2] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 06期

关键词：

D O I：

10.1038/ni.1607

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 (T beta RI) 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 T beta RI-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 T beta RI-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.

引用

页码：632 / 640

页数：9

共 51 条

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