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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4293-4302. Prepublished online as a Blood First Edition Paper on August 15, 2007; DOI 10.1182/blood-2007-05-088831. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-088831v1 110/13/4293    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yamazaki, S. Articles by Steinman, R. M. Search for Related Content PubMed PubMed Citation Articles by Yamazaki, S. Articles by Steinman, R. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 4, 2007 Accepted August 12, 2007 Dendritic cells are specialized accessory cells along with TGF- for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3- precursors Sayuri Yamazaki*, Anthony J. Bonito, Radek Spisek, Madhav Dhodapkar, Kayo Inaba, and Ralph M. Steinman Laboratory of Cellular Physiology and Immunology, and Chris Browne Center of Immunology and Immune Disease, The Rockefeller University, New York, NY, United States Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY, United States Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan * Corresponding author; email: yamazas{at}rockefeller.edu. Foxp3+CD25+CD4+ regulatory T cells are produced in the thymus (natural T regs) but can also differentiate from peripheral Foxp3-CD4+ precursors (induced or adaptive T regs). We assessed antigen presenting cell (APC) requirements for the latter differentiation. With added TGF-, both immature and mature populations of dendritic cells (DCs) induced antigen-specific Foxp3+ T regs from Foxp3- precursors. Using endogenous TGF-, DCs from gut-associated mesenteric lymph nodes were capable of differentiating Foxp3+T regs. Spleen DCs were 100 fold more potent than DC-depleted APCs for the induction of T regs and required 10-fold lower doses of peptide antigen. IL-2 was essential, but could be provided endogenously by T cells stimulated by DCs, but not other APCs. The required IL-2 was induced by DCs that expressed CD80/CD86 costimulatory molecules. The DC-induced Foxp3+T regs divided up to 6 times in 6 days and were comprised of CD62L and CD103 positive and negative forms. The induced Foxp3+T regs exerted suppression in vitro and blocked tumor immunity in vivo. These results indicate that DCs are specialized to differentiate functional peripheral Foxp3+T regs and help set the stage to use DCs to actively suppress the immune response in an antigen-specific manner. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Sehrawat, S. Suvas, P. P. Sarangi, A. Suryawanshi, and B. T. Rouse In Vitro-Generated Antigen-Specific CD4+ CD25+ Foxp3+ Regulatory T Cells Control the Severity of Herpes Simplex Virus-Induced Ocular Immunoinflammatory Lesions J. Virol., July 15, 2008; 82(14): 6838 - 6851. [Abstract] [Full Text] [PDF] L. Wang, K. Pino-Lagos, V. C. de Vries, I. Guleria, M. H. Sayegh, and R. J. Noelle Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells PNAS, July 8, 2008; 105(27): 9331 - 9336. [Abstract] [Full Text] [PDF] S. Sehrawat and B. T. Rouse Anti-Inflammatory Effects of FTY720 against Viral-Induced Immunopathology: Role of Drug-Induced Conversion of T Cells to Become Foxp3+ Regulators J. Immunol., June 1, 2008; 180(11): 7636 - 7647. [Abstract] [Full Text] [PDF] A. Ouabed, F.-X. Hubert, D. Chabannes, L. Gautreau, M. Heslan, and R. Josien Differential Control of T Regulatory Cell Proliferation and Suppressive Activity by Mature Plasmacytoid versus Conventional Spleen Dendritic Cells J. Immunol., May 1, 2008; 180(9): 5862 - 5870. [Abstract] [Full Text] [PDF] L. Van Overtvelt, E. Wambre, B. Maillere, E. von Hofe, A. Louise, A. M. Balazuc, B. Bohle, D. Ebo, C. Leboulaire, G. Garcia, et al. Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers J. Immunol., April 1, 2008; 180(7): 4514 - 4522. [Abstract] [Full Text] [PDF] R. K. Selvaraj and T. L. Geiger Mitigation of Experimental Allergic Encephalomyelitis by TGF-{beta} Induced Foxp3+ Regulatory T Lymphocytes through the Induction of Anergy and Infectious Tolerance J. Immunol., March 1, 2008; 180(5): 2830 - 2838. [Abstract] [Full Text] [PDF]

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