J. Exp. Med., Volume 188, Number 10, November 16, 1998 1831-1839

Overexpression of Natural Killer T Cells Protects V14-J281 Transgenic Nonobese Diabetic Mice against Diabetes

By Agnès Lehuen,^* Olivier Lantz,^* Lucie Beaudoin,^* Véronique Laloux,^* Claude Carnaud,^* Albert Bendelac, Jean-François Bach,^* and Renato C. Monteiro^*

From ^* INSERM U 25, Hôpital Necker, 75743 Paris, France; and the  Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Progression to destructive insulitis in nonobese diabetic (NOD) mice is linked to the failure of regulatory cells, possibly involving T helper type 2 (Th2) cells. Natural killer (NK) T cells might be involved in diabetes, given their deficiency in NOD mice and the prevention of diabetes by adoptive transfer of / double-negative thymocytes. Here, we evaluated the role of NK T cells in diabetes by using transgenic NOD mice expressing the T cell antigen receptor (TCR)  chain V14-J281 characteristic of NK T cells. Precise identification of NK1.1⁺ T cells was based on out-cross with congenic NK1.1 NOD mice. All six transgenic lines showed, to various degrees, elevated numbers of NK1.1⁺ T cells, enhanced production of interleukin (IL)-4, and increased levels of serum immunoglobulin E. Only the transgenic lines with the largest numbers of NK T cells and the most vigorous burst of IL-4 production were protected from diabetes. Transfer and cotransfer experiments with transgenic splenocytes demonstrated that V14-J281 transgenic NOD mice, although protected from overt diabetes, developed a diabetogenic T cell repertoire, and that NK T cells actively inhibited the pathogenic action of T cells. These results indicate that the number of NK T cells strongly influences the development of diabetes.

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• Hong, S., Van Kaer, L. (1999). Immune Privilege: Keeping an Eye on Natural Killer T Cells. J. Exp. Med. 190: 1197-1200 [Full Text]  
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• Wilson, S. B., Kent, S. C., Horton, H. F., Hill, A. A., Bollyky, P. L., Hafler, D. A., Strominger, J. L., Byrne, M. C. (2000). Multiple differences in gene expression in regulatory Valpha 24Jalpha Q T cells from identical twins discordant for type I diabetes. Proc. Natl. Acad. Sci. USA 97: 7411-7416 [Abstract] [Full Text]  
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