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Diabetes 55:179-185, 2006
DOI: 10.2337/diabetes.55.01.06.db05-0189
© 2006 by the American Diabetes Association
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Immunology and Transplantation

Transforming Growth Factor-ß and Natural Killer T-Cells Are Involved in the Protective Effect of a Bacterial Extract on Type 1 Diabetes

Marie-Alexandra Alyanakian1, Françoise Grela2, Aude Aumeunier2, Carlo Chiavaroli3, Christine Gouarin1, Emilie Bardel2, Gérard Normier3, Lucienne Chatenoud1, Nathalie Thieblemont2, and Jean-François Bach1

1 Université René Descartes Paris 5, Institut National de la Santé et de la Recherche Médicale U580, Hôpital Necker-Enfants Malades, Paris, France
2 Université René Descartes Paris 5, Unité Mixte de Recherche (UMR), National Center for Scientific Research (CNRS) 8147, Hôpital Necker-Enfants Malades, Paris, France
3 OM Pharma, Meyrin, Switzerland

Address correspondence and reprint requests to Jean-François Bach, MD, DSc, INSERM U580, Hôpital Necker-Enfants Malades, 161 Rue de Sèvres, 75015 Paris, France. E-mail: bach{at}necker.fr

Abbreviations: CFA, complete Freund’s adjuvant; IFA, incomplete Freund’s adjuvant; IFN-{gamma}, {gamma}-interferon; IL, interleukin; MDP, muramyldipeptide; NKT, natural killer T; TGF, transforming growth factor; TLR, Toll-like receptor

The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-ß. Natural killer T-cells also participate in the therapeutic effect because CD1d–/– NOD mice are partially resistant to the protective effect of OM-85. The question remains of the specificity of the protective effect of OM-85, which may include proinflammatory components. It will thus be important to further characterize the molecular components that afford protection from type 1 diabetes. Lipopolysaccharide is excluded, but other Toll-like receptor (TLR) agonists could be involved because OM-85 stimulated dendritic cells and induced TGF-ß production by splenocytes in a TLR-2–, TLR-4–, and MyD88-dependent fashion.


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Copyright © 2006 by the American Diabetes Association.