J Korean Med Sci.  2000 Apr;15(2):217-223. 10.3346/jkms.2000.15.2.217.

Defects in the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice

• Lee M
• Kim AY
• Kang Y

• KMID: 648127
• DOI: http://doi.org/10.3346/jkms.2000.15.2.217

Abstract

Due to their high immunostimulatory ability as well as the critical role they play in the maintenance of self-tolerance, dendritic cells have been implicated in the pathogenesis of autoimmune diseases. The non-obese diabetic (NOD) mouse is an animal model of autoimmune type 1 diabetes, in which pancreatic beta cells are selectively destroyed mainly by T cell-mediated immune responses. To elucidate initiation mechanisms of beta cell-specific autoimmunity, we attempted to generate bone marrow-derived dendritic cells from NOD mice. However, our results showed low proliferative response of NOD bone marrow cells and some defects in the differentiation into the myeloid dendritic cells. NOD dendritic cells showed lower expressions of MHC class II, B7-1, B7-2 and CD40, compared with C57BL/6 dendritic cells. In mixed lymphocyte reactions, stimulatory activities of NOD dendritic cells were also weak. Treatment with LPS, INF-gamma and anti-CD40 stimulated NOD dendritic cells to produce IL-12p70. The amount of IL-12, however, appeared to be lower than that of C57BL/6. Results of the present study indicated that there may be some defects in the development of NOD dendritic cells in the bone marrow, which might have an impact on the breakdown of self tolerance.

Keyword

Diabetes Mellitus; Dendritic Cells; Mice, Inbred NOD; Autoimmunity

MeSH Terms

Animal
Autoimmune Diseases/pathology
Autoimmune Diseases/immunology
Bone Marrow Cells/pathology*
Bone Marrow Cells/immunology*
Bone Marrow Cells/chemistry
Cell Differentiation/immunology
Cell Differentiation/drug effects
Dendritic Cells/pathology*
Dendritic Cells/immunology*
Dendritic Cells/chemistry
Diabetes Mellitus, Insulin-Dependent/pathology*
Diabetes Mellitus, Insulin-Dependent/immunology
Enzyme-Linked Immunosorbent Assay
Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
Interleukin-12/analysis
Interleukin-4/pharmacology
Lipopolysaccharides/pharmacology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Obesity