DEVELOPMENTAL PATHWAYS OF DENDRITIC CELLS IN-VIVO - DISTINCT FUNCTION, PHENOTYPE, AND LOCALIZATION OF DENDRITIC CELL SUBSETS IN FLT3 LIGAND-TREATED MICE

We have recently shown that Flt3 ligand administration dramatically in creases dendritic cell (DC) numbers in various mouse tissues. This has enabled the identification of distinct mature DC subpopulations. Thes e have been designate: population C (CD11c(bright)CD11b(bright)), D (C D11c(bright)CD11b(dull)), and E (CD11c(bright)CD11b(negative)). This r eport demonstrates that the mature DC subsets (C, D, and E) from Flt3 ligand-treated mice differ with respect to phenotype, geographic local ization, and function. The myeloid Ags CD11b, F3/80, and Ly-6C are pre dominantly expressed by population C, but not D or E. In addition, a s ubset of population C-type DC expresses 33D1 and CD4. In contrast, DC within population D and E selectively express the lymphoid-related DC markers CD8 alpha, DEC 205, CD1d, as well as CD23, elevated levels of CD117 (c-kit), CD24 (HSA), CD13, and CD54. Immunohistology indicates t hat the different DC subsets reside in distinct microenvironments, wit h populations D and E residing in the T cell areas of the white pulp, while DC within population C localize in the marginal zones. These DC subpopulations showed different capacities to phagocytose FITC-zymosan and to secrete IL-12 upon stimulation with Staphylococcus aureus cowa n I strain + IFN-gamma + granulocyte-macrophage-CSF. Population C-type DC were more phagocytic but secreted little inducible IL-12 while pop ulation D-and E-type DC showed poor phagocytic capacity and secreted c onsiderably higher levels of IL-12. These results underscore the impor tance of viewing DC development in vivo, as an interplay between disti nct lineages and a maturational dependence on specific microenvironmen tal signals.