NK T cells are a unique subset of T cells that recognize lipid antigens pre
sented by CD Id. After activation, NK T cells promptly produce large amount
s of cytokines, which may modulate the upcoming immune responses. Previous
studies have documented an association between decreased numbers of NK T ce
lls and the progression of some autoimmune diseases, suggesting that NK T c
ells may control the development of autoimmune diseases. To investigate the
role of NK T cells in autoimmune diabetes, we crossed CD1 knockout (CD1KO)
mutation onto the nonobese diabetic (NOD) genetic background. We found tha
t male CD1KO NOD mice exhibited significantly higher incidence and earlier
onset of diabetes compared with the heterozygous controls. The diabetic fre
quencies in female mice showed a similar pattern; however, the differences
were less profound between female CD1KO and control mice. Early treatment o
f NOD mice with (x-galactosylceramide, a potent NK T cell activator, reduce
d the severity of autoimmune diabetes in a CD1-dependent manner. Our result
s not only suggest a protective role of CD1-restricted NK T cells in autoim
mune diabetes but also reveal a causative link between the deficiency of NK
T cells and the induction of insulin-dependent diabetes mellitus.