NK dendritic cells expanded in IL-15 exhibit antitumor responses in vivo.
NK dendritic cells (NKDC) are a novel subtype of DC with NK cell properties. IL-15 is a pleiotropic cytokine that plays an obligate role in the proliferation and survival of NK cells. We hypothesized that IL-15 is also essential for NKDC development. NKDC were nearly absent in IL-15(-/-) mice, but restored by administration of exogenous IL-15. Treatment of wild-type mice with IL-15 caused a 2- to 3-fold expansion of both NK cells and NKDC. After 7 days of culture with IL-15, sorted splenic NKDC expanded 10-fold while NK cells increased 5-fold. NKDC expanded in IL-15 retained their cytolytic capacity but lost the ability to stimulate naive T cells. Meanwhile, NKDC expanded in IL-15 produced 10 times more IFN-gamma as fresh NKDC and conferred protection in a tumor prevention model. Thus, IL-15 is essential to the proliferation and survival of NKDC and IL-15 expanded NKDC possess antitumor properties.
Chaudhry
Umer I
UI
Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Plitas
George
G
Burt
Bryan M
BM
Kingham
T Peter
TP
Raab
Jesse R
JR
DeMatteo
Ronald P
RP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D019409:Interleukin-15