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The Journal of Immunology, 2005, 174: 1954-1961.
Copyright © 2005 by The American Association of Immunologists

Inhibition of T Cell Differentiation into Effectors by NKT Cells Requires Cell Contacts1

Jan Novak, Lucie Beaudoin, Thibault Griseri and Agnès Lehuen2

Institut National de la Santé de la Recherche Médicale Unité 561, Hôpital Cochin-Saint Vincent de Paul, 82 Avenue Denfert-Rochereau, 75014 Paris, France

NKT cells are potent regulatory T cells that prevent the development of several autoimmune diseases. Analysis of NKT cell regulatory function in the NOD mouse has revealed that NKT cells inhibit the development of type 1 diabetes by impairing the differentiation of anti-islet T cells into Th1 effector cells. In the present study, we have performed in vitro and in vivo experiments to determine the respective role of cytokines and cell contacts in the blockade of T cell differentiation by NKT cells. These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-{beta}, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-{beta}. In contrast, we show for the first time that cell contacts are crucial for the immunoregulatory function of NKT cells.




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