Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells

The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt 3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis, The flt3 ligand (flt3L) is a growth factor for hematopoi etic progenitors and induces hematopoietic progenitor and stem cell mobiliz ation in vivo. In addition, when mice are treated with flt3L immature B cel ls, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo . To further elucidate the role of flt3L in hematopoiesis, mice lacking flt 3L (flt3L-/-) were generated by targeted gene disruption. Leukocyte cellula rity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), an d spleen. Thymic cellularity, blood hematocrit, and platelet numbers were n ot affected. Significantly reduced numbers of myeloid and 8-lymphoid progen itors were noted in the BM of flt3L-/- mice. In addition a marked deficienc y of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c(++) CD8 alpha(-)) and l ymphoid-related (CD11c(++) CD8 alpha(+)) DC numbers were affected. We concl ude that flt3L has an important role in the expansion of early hematopoieti c progenitors and in the generation of mature peripheral leukocytes. (Blood , 2000;95: 3489-3497) (C) 2000 by The American Society of Hematology.