NK cells enhance the induction of CTL responses by IL-15 monocyte-derived dendritic cells.
Dendritic cells differentiated from monocytes (MoDC) in the presence of GM-CSF and IL-15 (IL-15 MoDC) exhibit superior migration and cytotoxic T-lymphocyte (CTL) induction compared with MoDC differentiated in IL-4 and GM-CSF (IL-4 MoDC) and are promising candidates for DC immunotherapy. We explored the mechanisms by which IL-15 MoDC induce CTL. IL-15 MoDC expressed higher levels of CD40 and secreted high levels of TNF-alpha, but little or no IL-12p70 compared with IL-4 MoDC. Despite immuno-selecting monocytes to >97% purity before MoDC generation, a tiny population (0.2%) of natural killer (NK) cells was identified that was increased sevenfold during IL-15 MoDC, but not IL-4 MoDC differentiation. These NK cells produced high levels of IFN-gamma and were responsible for the enhanced CTL-inducing capacity of the IL-15 MoDC, but not for their increased expression of CD40 or secretion of TNF-alpha. Interestingly, a proportion of IL-15 MoDC were found to express the NK cell marker, CD56, but these did not secrete IFN-gamma. These data implicate a role for small percentages of NK cells in the enhanced capacity of IL-15 MoDC to induce tumour-specific CTL independent of IL-12p70.
Hardy
Melinda Y
MY
Mater Medical Research Institute, South Brisbane, Queensland, Australia.
Kassianos
Andrew J
AJ
Vulink
Annelie
A
Wilkinson
Ray
R
Jongbloed
Sarah L
SL
Hart
Derek N J
DN
Radford
Kristen J
KJ
D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019013:CD40 Antigens; D019409:Interleukin-15; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor