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* Institut National de la Santé et de la Recherche Médicale Unité 561, University René Descartes Hôpital Cochin-Saint Vincent de Paul, Paris, France;
School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea;
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037; and
Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637
Invariant NKT (iNKT) cells can prevent diabetes by inhibiting the differentiation of anti-islet T cells. We recently showed that neither iNKT cell protection against diabetes nor iNKT cell inhibition of T cell differentiation in vitro requires cytokines such as IL-4, IL-10, IL-13, and TGF-
. In contrast, cell-cell contacts were required for iNKT cell inhibition of T cell differentiation in vitro. The present study was designed to determine whether the CD1d molecule is involved in the inhibitory function of iNKT cells. Experiments were performed in vitro and in vivo, using cells lacking CD1d expression. The in vivo experiments used CD1d-deficient mice that were either reconstituted with iNKT cells or expressed a CD1d transgene exclusively in the thymus. Both mouse models had functional iNKT cells in the periphery, even though CD1d was not expressed in peripheral tissues. Surprisingly, both in vitro inhibition of T cell differentiation by iNKT cells and mouse protection against diabetes by iNKT cells were CD1d-independent. These results reveal that iNKT cells can exert critical immunoregulatory effects in the absence of CD1d recognition and that different molecular interactions are involved in iNKT cell functions.
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1 This work was supported by grants from Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique, the French Ministry of Research, and the European Foundation for the Study of Diabetes (to A.L.). J.N. received fellowships from l’Association de Langue Française pour l’Etude du Diabète et des Maladies Métaboliques and la Fondation pour la Recherche Médicale. T.G. received a fellowship from the French Ministry of Research.
2 Current address: Center for the Research of Diabetes, Metabolism and Nutrition, 3rd Faculty of Medicine, Charles University, 128 08 Prague, Czech Republic.
3 J.N. and L.B. contributed equally to this work.
4 Address correspondence and reprint requests to Dr. Agnès Lehuen, Institut National de la Santé et de la Recherche Médicale Unité 561, Hôpital Cochin/Saint Vincent de Paul, 82 avenue Denfert-Rochereau, 75014 Paris, France. E-mail address: lehuen{at}paris5.inserm.fr
5 Abbreviations used in this paper: iNKT, invariant NKT; 
-GalCer, -galactosylceramide; pLck, proximal Lck; BM, bone marrow; WT, wild type.
This article has been cited by other articles:
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  L. T. Mars, A.-S. Gautron, J. Novak, L. Beaudoin, J. Diana, R. S. Liblau, and A. Lehuen Invariant NKT Cells Regulate Experimental Autoimmune Encephalomyelitis and Infiltrate the Central Nervous System in a CD1d-Independent Manner J. Immunol., August 15, 2008; 181(4): 2321 - 2329. [Abstract] [Full Text] [PDF]
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