GENERATION OR LARGE NUMBERS OF IMMATURE AND MATURE DENDRITIC CELLS FROM RAT BONE-MARROW CULTURES

We have defined conditions for generating large numbers of dendritic c ells (DC) in marrow cultures from 10-12-week-old ACI or WF rats. The c ombination of granulocyte-macrophage colony-stimulating factor (GM-CSF ) and TNF-alpha, known to induce DC from human CD34(+) progenitors, wa s not effective with rat. In contrast, GM-CSF plus IL-4 generated DG i n high yield, corresponding to 30-40 % of the initial number of plated marrow cells. The DC proliferated in distinctive aggregates, in which most cells had an immature phenotype marked by undetectable surface B 7 and high levels of MHC class II products within intracellular lysoso mes. When dislodged and dispersed, the aggregates gave rise to mature stellate DC with abundant surface MHC class II and B7, sparse MHC clas s II- lysosomes, and strong T cell-stimulating capacity. Therefore, ra t marrow progenitors can generate large numbers of immature DC, with a bundant intracellular MHC class II compartments, and potent, stimulato ry, mature DC.