NK cells enhance the induction of CTL responses by IL-15 monocyte-derived dendritic cells

• Published in: Immunology and cell biology Vol. 87; no. 8; pp. 606 - 614
• Main Authors: Hardy, Melinda Y, Kassianos, Andrew J, Vulink, Annelie, Wilkinson, Ray, Jongbloed, Sarah L, Hart, Derek N J, Radford, Kristen J
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2009; Blackwell Science Ltd
• Subjects: CD40 Antigens - immunology; CD40 Antigens - secretion; Cell Differentiation; Cells, Cultured; cytotoxic T lymphocytes; dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - secretion; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Humans; IL‐15; immunotherapy; Interleukin-15 - immunology; Interleukin-4 - immunology; Killer Cells, Natural - immunology; Monocytes - cytology; Monocytes - immunology; natural killer cells; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/icb.2009.44

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.