In vivo overexpression of Flt3 ligand expands and activates murine spleen natural killer dendritic cells.
Natural killer dendritic cells (NKDC) are a unique class of murine immune cells that possess the characteristics of both natural killer (NK) cells and dendritic cells (DC). Because NKDC are able to secrete IFN-gamma, directly lyse tumor cells, and present antigen to naïve T cells, they have immunotherapeutic potential. The relative paucity of NKDC, however, impedes their detailed study. We have found that in vivo, overexpression of the hematopoietic cytokine Flt3 ligand (Flt3L) expands NKDC in various organs from 2-18 fold. Flt3L expanded splenic NKDC retain the ability to lyse tumor cells and become considerably more potent at activating naïve allogeneic and antigen-specific T cells. Compared to normal splenic NKDC, Flt3L-expanded splenic NKDC have a more mature phenotype, a slightly increased ability to capture and process antigen, and a similar cytokine profile. In vivo, we found that Flt3L-expanded splenic NKDC are more effective than normal splenic NKDC in stimulating antigen-specific CD8 T cells. Additionally, we show that NKDC are able to cross-present antigen in vivo. The ability to expand NKDC in vivo using Flt3L will facilitate further analysis of their unique biology. Moreover, Flt3L-expanded NKDC may have enhanced immunotherapeutic potential, given their increased ability to stimulate T cells.
Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, Box 203, 1275 York Ave., New York, New York 10021, USA.
Umer I
UI
Chaudhry
Steven C
SC
Katz
T Peter
TP
Kingham
Venu G
VG
Pillarisetty
Jesse R
JR
Raab
Alaap B
AB
Shah
Ronald P
RP
DeMatteo
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005786:Gene Expression Regulation; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D039521:CD11c Antigen; D008565:Membrane Proteins; C084881:flt3 ligand protein