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A critical function for TGF-β signaling in the development of natural CD4CD25Foxp3 regulatory T cells

Nature Immunology, ISSN: 1529-2908, Vol: 9, Issue: 6, Page: 632-640
2008
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Article Description

The molecular mechanisms directing the development of 'natural' CD4CD25Foxp3 regulatory T cells (T 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 CD4CD25Foxp3 thymocytes at postnatal days 3-5. Paradoxically, however, beginning 1 week after birth, the same TβRI-mutant mice showed accelerated expansion of thymic CD4CD25Foxp3 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 CD4CD25Foxp3 cells from the thymus and periphery. Thus, transforming growth factor-β signaling is critical to the thymic development of natural CD4CD25Foxp3 T cells.

Bibliographic Details

Liu, Yongzhong; Zhang, Pin; Li, Jun; Kulkarni, Ashok B; Perruche, Sylvain; Chen, Wanjun

Springer Science and Business Media LLC

Medicine; Immunology and Microbiology

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