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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 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 Citation Map 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Dendritic cells are specialized accessory cells along with TGF-β for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3– precursors Sayuri Yamazaki1, Anthony J. Bonito1, Radek Spisek2, Madhav Dhodapkar2, Kayo Inaba3, and Ralph M. Steinman1 1 Laboratory of Cellular Physiology and Immunology and Chris Browne Center of Immunology and Immune Disease, and 2 Laboratory of Tumor Immunology and Immunotherapy, Rockefeller University, New York, NY; and 3 Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan 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 transforming growth factor (TGF)-β, both immature and mature populations of dendritic cells (DCs) induced antigen-specific Foxp3+ T regs from Foxp3– precursors. Using endogenous TGF-β, 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. Interleukin-2 (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: M. S. Turner, L. P. Kane, and P. A. Morel Dominant Role of Antigen Dose in CD4+Foxp3+ Regulatory T Cell Induction and Expansion J. Immunol., October 15, 2009; 183(8): 4895 - 4903. [Abstract] [Full Text] [PDF] M. Noris, P. Cassis, N. Azzollini, R. Cavinato, D. Cugini, F. Casiraghi, S. Aiello, S. Solini, L. Cassis, M. Mister, et al. The Toll-IL-1R Member Tir8/SIGIRR Negatively Regulates Adaptive Immunity against Kidney Grafts J. Immunol., October 1, 2009; 183(7): 4249 - 4260. [Abstract] [Full Text] [PDF] K. Sato, K. Eizumi, T. Fukaya, S. Fujita, Y. Sato, H. Takagi, M. Yamamoto, N. Yamashita, A. Hijikata, H. Kitamura, et al. 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