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 Immunoljournal_title
Nature immunologyauthors
Liu Y,Zhang P,Li J,Kulkarni AB,Perruche S,Chen Wdoi
10.1038/ni.1607subject
Has Abstractpub_date
2008-06-01 00:00:00pages
632-40issue
6eissn
1529-2908issn
1529-2916pii
ni.1607journal_volume
9pub_type
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