Ml. Drakes et al., IN-VIVO ADMINISTRATION OF FLT3 LIGAND MARKEDLY STIMULATES GENERATION OF DENDRITIC CELL PROGENITORS FROM MOUSE-LIVER, The Journal of immunology, 159(9), 1997, pp. 4268-4278
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.