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- Title
NK cells enhance the induction of CTL responses by IL-15 monocyte-derived dendritic cells.
- Authors
Hardy, Melinda Y.; Kassianos, Andrew J.; Vulink, Annelie; Wilkinson, Ray; Jongbloed, Sarah L.; Hart, Derek N. J.; Radford, Kristen J.
- Abstract
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-α, 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-γ 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-α. Interestingly, a proportion of IL-15 MoDC were found to express the NK cell marker, CD56, but these did not secrete IFN-γ. 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.
- Subjects
KILLER cells; DENDRITIC cells; BIOLOGICAL transport; LEUCOCYTES; TUMORS
- Publication
Immunology & Cell Biology, 2009, Vol 87, Issue 8, p606
- ISSN
0818-9641
- Publication type
Article
- DOI
10.1038/icb.2009.44