Immunotherapy of NOD mice with bone marrow-derived dendritic cells

We evaluated two bone marrow-derived dendritic cell (DC) populations from N OD mice, the murine model for type 1 human diabetes. DCs derived from GM-CS F [granulocyte/macrophage colony-stimulating factor] + interleukin (IL))-4 cultures expressed high levels of major histocompatibility complex (MHC) cl ass II, CD40, CD80, and CD86 molecules and were efficient stimulators of na ive allogeneic T-cells. In contrast, DCs derived from GM-CSF cultures had l ow levels of MHC class II costimulation/activation molecules, were able to take up mannosylated bovine serum albumin more efficiently than GM + IL-4 D Cs, and were poor T-cell stimulators. The two DC populations migrated to th e spleen and pancreas after intravenous injection. To determine the ability of the two DC populations to modulate diabetes development, DCs mere pulse d with a mixture of three islet antigen-derived peptides or with medium bef ore injection into prediabetic NOD mice. Despite phenotypic and functional differences in vitro, both populations prevented in vivo diabetes developme nt. Pulsing of the DCs with peptide in vitro did not significantly improve the ability of DCs to prevent disease, which suggests that DCs may process and present antigen to T-cells in vivo. In addition, we detected GAD65 pept ide-specific IgG1 antibody responses in DC-treated mice. Overall, these res ults suggest that a Th2 response was generated in DC-treated mice. This res ponse was optimal when using GR I + IL-4 DCs, which suggests that the balan ce between regulatory Th2 and effector Th1 cells may have been altered in t hese mice.