Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation

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  • Bertrand Dubois
    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.
  • Ludivine Chapat
    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.
  • Anne Goubier
    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.
  • Martine Papiernik
    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.
  • Jean-François Nicolas
    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.
  • 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.

抄録

<jats:title>Abstract</jats:title><jats:p>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 γ (IFNγ) 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.</jats:p>

収録刊行物

  • Blood

    Blood 102 (9), 3295-3301, 2003-11-01

    American Society of Hematology

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