FLT3 LIGAND INDUCES THE GENERATION OF FUNCTIONALLY ACTIVE DENDRITIC CELLS IN MICE

FLT3 ligand (FL) is a recently described, hematopoietic growth factor that stimulates the proliferation and differentiation of hematopoietic progenitors. We have investigated the effect of FL on murine hematopo iesis and dendritic cell (DC) generation and accumulation in lymphoid tissues and liver in vivo and in vitro evaluating the morphologic, phe notypic, and functional characteristics of these DC. We have observed extramedullary hematopoiesis in the mouse spleen with all lineages of hematopoietic cells represented after the administration of FL. Inject ion of FL results in a time-dependent and reversible accumulation of D C in the spleen, bone marrow, lymph nodes, and liver. Both. flow cytom etry and immunohistochemistry revealed a significant accumulation of D C in these tissues. Results of mixed leukocyte reaction suggested that these cells, isolated from murine bone marrow or spleen, were active as antigen presenting cells, Furthermore, cultivation of splenic and m arrow cells with GM-CSF and IL-4 gave rise to large numbers of functio nally active mature DC, Thus, the results of this study suggest that F L is a promising growth factor that stimulates the generation of large number of DC and may be a useful cytokine for the immunotherapy of ca ncer. (C) 1997 Academic Press.