Immunophenotypic and ultrastructural differentiation and maturation of nonlymphoid dendritic cells in osteopetrotic (op) mice with the total absence of macrophage colony stimulating factor activity.

The effect of the op/op mutation on the development of DCs including IDCs in the thymus and peripheral lymphoid tissues and epidermal LCs or IDDCs was determined in order to assess the differentiation of such cells in vivo in the absence of M-CSF. op/op and littermate control mice were examined by immunohistochemistry using F4/80, BM8, NLDC-145, M1-8, MIDC-8, and M5/114. In contrast with the fact that the monocytic cell series, monocyte-derived macrophages and osteoclasts were deficient, DCs in the lymphoid tissues and epidermal LCs from op/op mice showed similar immunoreactivities to those of normal littermates and no statistically significant differences in their numbers compared to the normal littermates. Further, the epidermal LCs in the mutant mice stained positively with the histochemical stains for ADPase or ATPase. The development of tubulovesicular system in IDCs and the presence of Birbeck granules in LCs of the op/op mice were confirmed by electron microscopy but the cytoplasmic projection of these cells was not prominent. From these results, we concluded that the development and differentiation of DCs are influenced not by M-CSF but by GM-CSF. In our in vitro study, however, we found that GM-CSF-dependent macrophages do not resemble DCs ultrastructurally, suggesting that besides GM-CSF, some other cytokines are necessary for the differentiation and maturation of DCs.