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.