The Diabetes Type 1 Locus Idd6 Modulates Activity of CD4+CD25+ Regulatory T-Cells
- Ute Christine Rogner1,
- Françoise Lepault2,
- Marie-Claude Gagnerault2,
- David Vallois2,
- Joëlle Morin2,
- Philip Avner1 and
- Christian Boitard2
- 1Unité de Génétique Moléculaire Murine, Centre National de Recherche (CNRS) Unité de Recherche Associée (URA) 2578, Institut Pasteur, Paris, France
- 2Hôpital Cochin St. Vincent de Paul, Paris, France
- Address correspondence and reprint requests to Dr. U.C. Rogner, Génétique Moléculaire Murine, CNRS URA 2578, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. E-mail: urogner{at}pasteur.fr
Abstract
The genetic locus Idd6 confers susceptibility to the spontaneous development of type 1 diabetes in the NOD mouse. Our studies on disease resistance of the congenic mouse strain NOD.C3H 6.VIII showed that Idd6 influences T-cell activities in the peripheral immune system and suggest that a major mechanism by which the Idd6 locus modifies diabetes development is via modulation of regulatory T-cell activities. Our transfer experiments using total splenocytes and purified T-cells demonstrated that the locus specifically controls the efficiency of disease protection mediated by the regulatory CD4+CD25+ T-cell subset. Our data also implicate the Idd6 locus in controlling the balance between infiltrating lymphocytes and antigen-presenting cells within the pancreatic islet.
Footnotes
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U.C.R. and F.L. contributed equally to this study.
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- Accepted October 12, 2005.
- Received May 10, 2005.
- DIABETES
