Immunotherapy of NOD mice with bone marrow-derived dendritic cells.
We evaluated two bone marrow-derived dendritic cell (DC) populations from NOD mice, the murine model for type 1 human diabetes. DCs derived from GM-CSF [granulocyte/macrophage colony-stimulating factor] + interleukin (IL)-4 cultures expressed high levels of major histocompatibility complex (MHC) class II, CD40, CD80, and CD86 molecules and were efficient stimulators of naive allogeneic T-cells. In contrast, DCs derived from GM-CSF cultures had low levels of MHC class II costimulation/activation molecules, were able to take up mannosylated bovine serum albumin more efficiently than GM + IL-4 DCs, and were poor T-cell stimulators. The two DC populations migrated to the spleen and pancreas after intravenous injection. To determine the ability of the two DC populations to modulate diabetes development, DCs were pulsed with a mixture of three islet antigen-derived peptides or with medium before injection into prediabetic NOD mice. Despite phenotypic and functional differences in vitro, both populations prevented in vivo diabetes development. 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 peptide-specific IgG1 antibody responses in DC-treated mice. Overall, these results suggest that a Th2 response was generated in DC-treated mice. This response was optimal when using GM + IL-4 DCs, which suggests that the balance between regulatory Th2 and effector Th1 cells may have been altered in these mice.
Feili-Hariri
M
M
Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
Dong
X
X
Alber
S M
SM
Watkins
S C
SC
Salter
R D
RD
Morel
P A
PA
D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D001854:Bone Marrow Cells; D019013:CD40 Antigens / Q000032:analysis; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology / Q000637:transplantation*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D016688:Mice, Inbred NOD; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D018122:B7-1 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012710:Serum Albumin, Bovine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor