Immunobiology of DC in NOD mice

NOD mice spontaneously develop diabetes between 15 and 20 weeks of age, whi ch is preceded by insulitis characterized by the infiltration of lymphocyte s, Dendritic cells (DC) are among the first cells to infiltrate the islet a nd they have been implicated in the pathogenesis of the disease. Our work h as been concerned with the detailed characterization of four distinct DC po pulations in NOD mice: two derived from bone marrow (BM) cells cultured in either granulocyte-macrophage colony-stimulating factor (GM-CSF) plus inter leukin-4 (IL-4) or GM-CSF alone and two from the spleen of Flt3 ligand (FLt 3L)-treated mice, isolated on the basis of CD8 alpha expression. Phenotypic and functional differences between these DC subsets in NOD mice have been identified, in addition, we obtained a lower yield of NOD BM-derived DC and they expressed higher levels of cell-surface CD40 and IL-12 p40 mRNA than BM-derived DC from the diabetes-resistant strain, B10.BR. We have also inve stigated the ability of these DC populations to modulate the development an d progression of diabetes in NOD mice.