In vivo overexpression of Flt3 ligand expands and activates murine spleen natural killer dendritic cells

Natural killer dendritic cells ( NKDC) are a unique class of murine immune cells that possess the characteristics of both natural killer ( NK) cells and dendritic cells ( DC). Because NKDC are able to secrete IFN-gamma, directly lyse tumor cells, and present antigen to naive T cells, they have immunotherapeutic potential. The relative paucity of NKDC, however, impedes their detailed study. We have found that in vivo, overexpression of the hematopoietic cytokine Flt3 ligand ( Flt3L) expands NKDC in various organs from 2-18 fold. Flt3L expanded splenic NKDC retain the ability to lyse tumor cells and become considerably more potent at activating naive allogeneic and antigen-specific T cells. Compared to normal splenic NKDC, Flt3L-expanded splenic NKDC have a more mature phenotype, a slightly increased ability to capture and process antigen, and a similar cytokine profile. In vivo, we found that Flt3L-expanded splenic NKDC are more effective than normal splenic NKDC in stimulating antigen-specific CD8 T cells. Additionally, we show that NKDC are able to cross-present antigen in vivo. The ability to expand NKDC in vivo using Flt3L will facilitate further analysis of their unique biology. Moreover, Flt3L-expanded NKDC may have enhanced immunotherapeutic potential, given their increased ability to stimulate T cells.