CD1-restricted NK T Cells Protect Nonobese Diabetic Mice from Developing Diabetes

doi:10.1084/jem.194.3.313

Published online 6 August 2001. doi:10.1084/jem.194.3.313

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© The Rockefeller University Press, 0022-1007/2001/8/313/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 3, August 6, 2001 313-320

Original Article

CD1-restricted NK T Cells Protect Nonobese Diabetic Mice from Developing Diabetes

Bin Wang^a, Yan-Biao Geng^a, and Chyung-Ru Wang^a
^a Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology, and Department of Pathology, University of Chicago, Chicago, IL 60637

Correspondence to: Chyung-Ru Wang, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 924 East 57th St., Rm. 412, Chicago, IL 60637-5420. Tel:773-702-4725 Fax:773-702-1576 E-mail:cwang{at}midway.uchicago.edu.

NK T cells are a unique subset of T cells that recognize lipidantigens presented by CD1d. After activation, NK T cells promptlyproduce large amounts of cytokines, which may modulate the upcomingimmune responses. Previous studies have documented an associationbetween decreased numbers of NK T cells and the progressionof some autoimmune diseases, suggesting that NK T cells maycontrol the development of autoimmune diseases. To investigatethe role of NK T cells in autoimmune diabetes, we crossed CD1knockout (CD1KO) mutation onto the nonobese diabetic (NOD) geneticbackground. We found that male CD1KO NOD mice exhibited significantlyhigher incidence and earlier onset of diabetes compared withthe heterozygous controls. The diabetic frequencies in femalemice showed a similar pattern; however, the differences wereless profound between female CD1KO and control mice. Early treatmentof NOD mice with ${alpha}$ -galactosylceramide, a potent NK T cell activator,reduced the severity of autoimmune diabetes in a CD1-dependentmanner. Our results not only suggest a protective role of CD1-restrictedNK T cells in autoimmune diabetes but also reveal a causativelink between the deficiency of NK T cells and the inductionof insulin-dependent diabetes mellitus.

Key Words: CD1, NK T cells, autoimmunity, diabetes, cytokines

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