IN-VIVO ADMINISTRATION OF FLT3 LIGAND MARKEDLY STIMULATES GENERATION OF DENDRITIC CELL PROGENITORS FROM MOUSE-LIVER

The study of liver dendritic cells (DC) and their progenitors is restr icted by the small numbers that can be isolated or propagated from nor mal hepatic tissue, We examined the Ex vivo growth, phenotype, and fun ction of these cells after the administration to mice of the recently cloned hemopoietic growth factor flt3 ligand (FL), which is highly eff ective in mobilizing stem/progenitor cells, FL treatment (10 mu g/day for 10 days) resulted ina mean 14-fold increase in the absolute number of nonparenchymal cells recovered from collagenase-digested livers co mpared with the control value, Culture of these nonparenchymal cells i n granulocyte-macrophage CSF (GM-CSF; 1000 U/ml) resulted in the early formation of proliferating cell clusters and maximal release (within 4-5 days) of markedly increased numbers of nonadherent, low buoyant de nsity cells per liver, Maximal release of low buoyant density cells pr opagated from control livers tvas at the later time of 6 to 8 days, Ce lls from both sources were DEC-205(+), CD11c(+), MHC class II+, CD80(l ow) (i.e., low level of CD80), CD86(low) and CD40(low). This immature phenotype was linked to poor T cell allostimulatory activity, indicati ve of DC progenitors, Propagation of cells from livers of Fe-treated m ice in GM-CSF and IL-4 resulted in a more mature DC phenotype and func tion, Maturational changes were also observed following exposure of th e GM-CSF-stimulated progenitors to type 1 collagen for 3 additional da ys, alta? ability of FL to boost production of large numbers of Liver DC progenitors provides opportunities for the further study of these i mportant APC in normal liver immunobiology and in immune-mediated hepa tic disorders.