DENDRITIC CELL PROGENITORS PHAGOCYTOSE PARTICULATES, INCLUDING BACILLUS-CALMETTE-GUERIN ORGANISMS, AND SENSITIZE MICE TO MYCOBACTERIAL ANTIGENS IN-VIVO

Dendritic cells, while effective in sensitizing T cells to several dif ferent antigens, show little or no phagocytic activity. To the extent that endocytosis is required for antigen processing and presentation, it is not evident how dendritic cells would present particle-associate d peptides. Evidence has now been obtained showing that progenitors to dendritic cells can internalize particles, including Bacillus Calmett e-Guerin (BCG) mycobacteria. The particulates are applied for 20 h to bone marrow cultures that have been stimulated with granulocyte/macrop hage colony-stimulating factor (GM-CSF) to induce aggregates of growin g dendritic cells. Cells within these aggregates are clearly phagocyti c. If the developing cultures are exposed to particles, washed, and '' chased'' for 2 d, the number of major histocompatibility complex class II-rich dendritic cells increases substantially and at least 50% cont ain internalized mycobacteria or latex particles. The mycobacteria-lad en, newly developed dendritic cells are much more potent in presenting antigens to primed T cells than corresponding cultures of mature dend ritic cells that are exposed to a pulse of organisms. A similar situat ion exists when the BCG-charged dendritic cells are injected into the footpad or blood stream of naive mice. Those dendritic cells that have phagocytosed organisms induce the strongest T cell responses to mycob acterial antigens in draining lymph node and spleen. The administratio n of antigens to GM-CSF-induced, developing dendritic cells (by increa sing both antigen uptake and cell numbers) will facilitate the use of these antigen-presenting cells for active immunization in situ.