In Vivo Role of Flt3 Ligand and Dendritic Cells in NK Cell Homeostasis

Abstract

IL-15 is required for NK cell development and homeostasis in vivo. Because IL-15 is presented in trans via its high-affinity IL-15Rα–chain to cells expressing the IL-15Rβγ complex, we postulated that certain IL-15–bearing cells must be required for NK cell homeostasis. Using IL-15WT/WT and IL-15−/− mice, bone marrow chimeras with normal cellularity, and a selective depletion of CD11chi dendritic cells (DCs), we demonstrate that ablation of the resting CD11chi DC population results in a highly significant decrease in the absolute number of mature NK cells. In contrast, administration of Flt3 ligand increases the CD11chi DC population, which, when expressing IL-15, significantly expands mature NK cells via enhanced survival and proliferation. In summary, a CD11chi DC population expressing IL-15 is required to maintain NK cell homeostasis under conditions of normal cellularity and also is required to mediate Flt3 ligand-induced NK cell expansion in vivo.