Qualitative and quantitative abnormalities in splenic dendritic cell populations in NOD mice.
The phenotype and function of splenic DC populations from diabetes-prone NOD mice were characterized and compared to DC from diabetes-resistant strains in the presence or absence of Flt3 ligand (FL) treatment. NOD mice were found to have significantly fewer CD8alpha+ DC than both B10.BR and C57BL/6 mice, and this defect was reversed by FL treatment. Freshly isolated CD8alpha+ and CD8alpha- DC from all three strains were found to express similar levels of costimulatory molecules and this was similar in both FL-treated and untreated animals. IL-12 p40 production was significantly lower in purified CD11c+ DC from NOD mice compared to DC from C57BL/6 or B10.BR mice. CD8alpha+ DC isolated from NOD mice produced lower levels of IL-12p40 than CD8alpha+ DC from C57CBL/6 and this was dependent on the nature of the stimulus given. In contrast both CD8alpha+ and CD8alpha- DC from FL-treated mice produced high levels of IL-12p40 following activation, but only the CD8alpha- DC produced IL-12p70. Functionally, freshly isolated CD8alpha- DC were more stimulatory than CD8alpha+ DC in a primary allogeneic mixed lymphocyte reaction. However, DC maturation resulted in increased T cell stimulatory capacity for both DC subsets, and this pattern was seen in all strains. These results demonstrate significant differences in phenotype and function of splenic NOD CD8alpha+ DC, and further suggest that FL treatment may reverse some of these abnormalities.
Vasquez
A C
AC
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Feili-Hariri
M
M
Tan
R J
RJ
Morel
P A
PA
D000276:Adjuvants, Immunologic; D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D016130:Immunophenotyping / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D021122:Protein Subunits / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000276:Adjuvants, Immunologic; D039521:CD11c Antigen; D016827:CD8 Antigens; D053762:Interleukin-12 Subunit p40; D008565:Membrane Proteins; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D018664:Interleukin-12; D007371:Interferon-gamma