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

Due to their high immunostimulatory ability as well as the critical role th ey play in the maintenance of self-tolerance, dendritic cells have been imp licated in the pathogenesis of autoimmune diseases. The non-obese diabetic (NOD) mouse is an animal model of autoimmune type 1 diabetes, in which panc reatic beta cells are selectivly destroyed mainly by T cell-mediated immune responses. To elucidate initiation mechanisms of beta cell-specific autoim munity, we attempted to generate bone marrow-derived dendritic cells from N OD mice. However, our results showed low proliferative response of NOD bone marrow cells and some defects in the differentiation into the myeloid dend ritic 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 lympho cyte reactions, stimulatory activities of NOD dendritic cells were also wea k. Treatment with LPS, INF-gamma and anti-CD40 stimulated NOD dendritic cel ls 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 marr ow, which might have an impact on the breakdown of self tolerance.