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Transforming growth factor-β and T-cell-mediated immunoregulation in the control of autoimmune diabetes

Authors

  • Sylvaine You,

    1. Université René Descartes Paris 5, Institut National de la Santé et de la Recherche Médicale U580 and Hôpital Necker-Enfants Malades, Paris, France.
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  • Nathalie Thieblemont,

    1. Université René Descartes Paris 5, CNRS, UMR 8147, Hôpital Necker-Enfants Malades, Paris, France.
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  • Marie-Alexandra Alyanakian,

    1. Université René Descartes Paris 5, Institut National de la Santé et de la Recherche Médicale U580 and Hôpital Necker-Enfants Malades, Paris, France.
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  • Jean-François Bach,

    1. Université René Descartes Paris 5, Institut National de la Santé et de la Recherche Médicale U580 and Hôpital Necker-Enfants Malades, Paris, France.
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  • Lucienne Chatenoud

    Corresponding author
    1. Université René Descartes Paris 5, Institut National de la Santé et de la Recherche Médicale U580 and Hôpital Necker-Enfants Malades, Paris, France.
      Lucienne Chatenoud M.D., D.Sc.
      INSERM U580
      Hôpital Necker-Enfants Malades
      161 Rue de Sèvres
      75015 Paris
      France
      Tel.: +33 1 44495373
      Fax: +33 1 43062388
      Email: chatenoud@necker.fr
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Lucienne Chatenoud M.D., D.Sc.
INSERM U580
Hôpital Necker-Enfants Malades
161 Rue de Sèvres
75015 Paris
France
Tel.: +33 1 44495373
Fax: +33 1 43062388
Email: chatenoud@necker.fr

Abstract

Summary:  It is now well-established that CD4+ regulatory T cells are instrumental in controlling immune responses both to self-antigens and to non-self-antigens. However, the precise modalities involved in their differentiation and survival, their mode of action and their antigen specificity are only partially understood. We have been particularly interested in the study of regulatory T cells controlling autoimmune insulin-dependent diabetes. Here, we provide evidence to support the phenotypic and functional diversity of regulatory T cells mediating transferable ‘active’ or ‘dominant’ peripheral tolerance in the non-obese diabetic mouse model (NOD). They include natural and adaptive regulatory T cells that are operational both in unmanipulated NOD mice and in animals undergoing treatments aimed at inducing/restoring tolerance to self-β-cell antigens. At least in our hands, the differential cytokine-dependency appears as a major distinctive feature of regulatory T cells subsets. Among immunoregulatory cytokines, transforming growth factor-β(TGF-β) appeared to play a key role. Herein we discuss these results and the working hypothesis they evoke in the context of the present literature, where the role of TGF-β-dependent T-cell-mediated immunoregulation is still debated.

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