Abstract 533: Dendritic cells are professional educators of Natural Killer cells

Abstract

Abstract Dendritic cells (DCs) and Natural Killer (NK) cells are important components of innate immunity. NK cells are the principal effectors of the innate immune system and play an important role in tumor surveillance and anti-viral immunity. It has been commonly accepted that CD56bright NK cells are the main source of cytokine production while CD56dim are mostly responsible for cytolytic activity and target cell killing. CD56dim NK cells acquire KIR (Killer cell Immunoglobulin-like Receptors or KIR) receptors by a process called NK cell education or licensing. NK cell education has been defined as the mechanism by which NK cell acquire inhibitory KIR and how signaling by specific cognate ligands leads to gain of NK cell function. DCs are antigen presenting cells which act as sentinels for the immune system by engulfing pathogens, processing and presenting them to CD4 and CD8 T cells. Interactions between dendritic cells and natural killer cells have been extensively studied but the role that DCs might play in NK cell education remains elusive and poorly understood. We evaluated the in-vitro interaction between adult monocyte-derived dendritic cells and natural killers cells from healthy donors. Mature monocyte-derived dendritic cells (mdDCs) were co-cultured with KIR negative and KIR positive NK cells in addition to different concentrations of IL-15. After 5 days of co-culture; the KIR negative population (0.8% KIR positive after 5 days of co-cultured) acquired up to 3.8% KIR expression when co-cultured with mdDCs (1:1 ratio) and 0.5 ng/mL of IL-15. In addition, a population of NK cells which expressed 28% KIR after 5 days of culture expressed up to 38% KIR when mdDCs and 0.5 ng/mL of IL-15 were added to the culture. Of note, enhanced KIR expression (as a marker of maturation) required both IL-15 and mdDcs as no effect was seen when mdDcs or IL-15 were added alone. Aside from the differences noted in KIR expression, a population of CD56dim NK cells became CD56bright when both KIR negative (8.44% to 23.6%) and KIR positive (0.8% to 24.9%) NK cells were co-cultured with mdDCs and IL-15. In conclusion, our studies suggest that dendritic cells have the ability to educate NK cells and that this process is dependent on IL-15, which can be trans-presented through IL-15Rα on DCs. Dendritic cells in addition to IL-15 may also revert a population of mature CD56dim NK cells to a CD56bright NK cells, which are considered less differentiated, suggesting that NK maturation can be bidirectional and may exhibit more plasticity than previously recognized. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 533. doi:1538-7445.AM2012-533