51. NK cells enhance the induction of CTL responses by IL-15 monocyte-derived dendritic cells.
- Author
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Hardy MY, Kassianos AJ, Vulink A, Wilkinson R, Jongbloed SL, Hart DN, and Radford KJ
- Subjects
- CD40 Antigens immunology, CD40 Antigens metabolism, Cell Differentiation, Cells, Cultured, Dendritic Cells metabolism, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Humans, Interleukin-4 immunology, Monocytes cytology, Dendritic Cells cytology, Dendritic Cells immunology, Interleukin-15 immunology, Killer Cells, Natural immunology, Monocytes immunology, T-Lymphocytes, Cytotoxic immunology
- 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-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.
- Published
- 2009
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