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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3295-3301. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-03-0727. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0727v1 102/9/3295    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 Dubois, B. Articles by Kaiserlian, D. Search for Related Content PubMed PubMed Citation Articles by Dubois, B. Articles by Kaiserlian, D. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation Bertrand Dubois, Ludivine Chapat, Anne Goubier, Martine Papiernik, Jean-François Nicolas, and Dominique Kaiserlian From the Department of Immunité et Vaccination, Institut National de la Santé et de la Recherche Médicale (INSERM) U404, Institut Fédératif de Recherche (IFR) 128 Bioscience Lyon Gerland, Lyon, France; INSERM U591, Centre Hospitalier Universitaire (CHU) Necker-Enfants Malades, Paris, France; Department of Immunobiologie Fondamentale et Clinique, INSERM U503, IFR 128 Bioscience Lyon Gerland, Lyon, France. To elucidate the role of CD4+CD25+ regulatory T cells in oral tolerance, we used the model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB), which is mediated by CD8+ Tc1 effector cells independently of CD4+ T-cell help. Conversely to normal mice, invariant chain knock-out (KO) (Ii°/°) mice, which are deficient in CD4+ T cells, cannot be orally tolerized and develop a chronic hapten-specific CHS response. Transfer of naive CD4+ T cells before hapten gavage into Ii°/° mice restores oral tolerance by a mechanism independent of interleukin-10 (IL-10) production by CD4+ T cells. That naturally occurring CD4+CD25+ T cells are critical for oral tolerance induction is demonstrated by the finding that (1) transfer of CD4+CD25+ but not CD4+CD25– T cells into Ii°/° recipients completely prevents the CHS response and skin infiltration by CD8+ T cells, by blocking development of hapten-specific CD8+ T cells; (2) in vivo depletion of CD4+CD25+ cells by antibody treatment in normal mice impairs oral tolerance; and (3) CD4+CD25+ T cells inhibit hapten-specific CD8+ T-cell proliferation and interferon (IFN) production, in vitro. These data show that naturally occurring CD4+CD25+ T cells are instrumental for orally induced tolerance and are key actors for the control of antigen-specific CD8+ T-cell effectors mediating skin inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Hacini-Rachinel, S. Nancey, G. Boschetti, F. Sardi, R. Doucet-Ladeveze, P.-Y. Durand, B. Flourie, and D. 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