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

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)...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2010-03, Vol.184 (6), p.2769-2775
Main Authors: Guimond, Martin, Freud, Aharon G, Mao, Hsiaoyin C, Yu, Jianhua, Blaser, Bradley W, Leong, Jeffrey W, Vandeusen, Jeffrey B, Dorrance, Adrienne, Zhang, Jianying, Mackall, Crystal L, Caligiuri, Michael A
Format: Article
Language:English
Subjects:
Animals
CD11c Antigen - biosynthesis
Cell Differentiation - immunology
Cell Proliferation
Cell Survival - immunology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Female
Homeostasis - immunology
Humans
Interleukin-15 - deficiency
Interleukin-15 - genetics
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
Killer Cells, Natural - transplantation
Ligands
Membrane Proteins - administration & dosage
Membrane Proteins - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Recombinant Proteins - administration & dosage
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0900685