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In Vivo Role of Flt3 Ligand and Dendritic Cells in NK Cell Homeostasis JOURNAL OF IMMUNOLOGY Guimond, M., Freud, A. G., Mao, H. C., Yu, J., Blaser, B. W., Leong, J. W., Vandeusen, J. B., Dorrance, A., Zhang, J., Mackall, C. L., Caligiuri, M. A. 2010; 184 (6): 2769-2775

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-15Ralpha-chain to cells expressing the IL-15Rbetagamma complex, we postulated that certain IL-15-bearing cells must be required for NK cell homeostasis. Using IL-15(WT/WT) and IL-15(-/-) mice, bone marrow chimeras with normal cellularity, and a selective depletion of CD11c(hi) dendritic cells (DCs), we demonstrate that ablation of the resting CD11c(hi) DC population results in a highly significant decrease in the absolute number of mature NK cells. In contrast, administration of Flt3 ligand increases the CD11c(hi) DC population, which, when expressing IL-15, significantly expands mature NK cells via enhanced survival and proliferation. In summary, a CD11c(hi) 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.

View details for DOI 10.4049/jimmunol.0900685

View details for Web of Science ID 000275389000005

View details for PubMedID 20142363