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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-03-0727. This Article 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 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. Social Bookmarking                   What's this? Submitted March 7, 2003 Accepted July 1, 2003 Innate CD4+CD25+ regulatory T cells are required for oral tolerance and control CD8+ T cells mediating skin inflammation Bertrand Dubois, Ludivine Chapat, Anne Goubier, Martine Papiernik, Jean-Francois Nicolas, and Dominique Kaiserlian* Immunite et Vaccination, INSERM, Unite 404, Lyon, France INSERM, Unite 345, Paris, France Immunobiologie fondamentale et clinique, INSERM, Unite 503, Lyon, France * Corresponding author; email: kaiserlian{at}cervi-lyon.inserm.fr. To elucidate the role of CD4+CD25+ regulatory T cells in oral tolerance, we used the model of contact hypersensitivity (CHS) to DNFB, which is mediated by CD8+ Tc1 effector cells independently of CD4+ T cell help. Conversely to normal mice, invariant chain 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 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: (i) 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, (ii) in vivo depletion of CD4+CD25+ cells by antibody treatment in normal mice impairs oral tolerance and (iii) CD4+CD25+ T cells inhibit hapten-specific CD8+ T cell proliferation and 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? 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