A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.
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.
Liu
Yongzhong
Y
Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zhang
Pin
P
Li
Jun
J
Kulkarni
Ashok B
AB
Perruche
Sylvain
S
Chen
Wanjun
W
D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D053264:B-Cell Activating Factor; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta