title: 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.
authors.affiliation: Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Pin
authors.initials: P
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: Sylvain
authors.initials: S
authors.lastname: Perruche
authors.forename: Wanjun
authors.initials: W
authors.lastname: Chen
mesh_terms: 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*
chemical_list: D053264:B-Cell Activating Factor; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta