Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse

Quantitative and qualitative defects in CD1-restricted natural killer T cel ls have been reported in several autoimmune-prone strains of mice, includin g the nonobese diabetic (NOD) mouse. These defects are believed to be assoc iated with the emergence of spontaneous autoimmunity. Here we demonstrate t hat both CD1d-null NOD and CD1d-null NOD/BDC2.5 T cell receptor transgenic mice have an accelerated onset and increased incidence of diabetes when com pared with CD1d(+/-) and CD1d(+/+) littermates, The acceleration of disease did not seem to result from changes in the T helper (Th)1/Th2 balance beca use lymphocytes purified from lymphoid organs and pancreatic islets of wild -type and CD1d-null mice secreted equivalent amounts of IFN-gamma and IL-4 after stimulation. In contrast, the pancreata of CD1d-null mice harbored si gnificantly higher numbers of activated memory T cells expressing the chemo kine receptor CCR4, Notably, the presence of these T cells was associated w ith immunohistochemical evidence of increased destructive insulitis, Thus, CD1d-restricted T cells are critically important for regulation of the spon taneous disease process in NOD mice.