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) 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.
Department of Molecular Virology, The Ohio State University, Columbus, OH43210, USA.
Martin
M
Guimond
Aharon G
AG
Freud
Hsiaoyin C
HC
Mao
Jianhua
J
Yu
Bradley W
BW
Blaser
Jeffrey W
JW
Leong
Jeffrey B
JB
Vandeusen
Adrienne
A
Dorrance
Jianying
J
Zhang
Crystal L
CL
Mackall
Michael A
MA
Caligiuri
D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D008024:Ligands; D008565:Membrane Proteins / Q000008:administration & dosage / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000008:administration & dosage
D039521:CD11c Antigen; D019409:Interleukin-15; D008024:Ligands; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein