Liver plasmacytoid dendritic cells stimulate NK1.1+ cells (82.12)

Abstract

Abstract Introduction: Plasmacytoid dendritic cells (pDC) play a central role in innate immunity. While much is known about spleen pDC, liver pDC has only been recently identified and their function remains largely unknown. We sought to determine the ability of liver pDC to stimulate NK1.1+ cells in vitro in comparison to spleen pDC. Methods: Liver and spleen pDC (CD11c+B220+NK1.1−CD19−CD11b−) from C57BL/6 mice were expanded in vivo with an adenovirus encoding murine Flt3L cDNA and isolated by fluorescence activated cell sorting. These cells were co-cultured with spleen NK1.1+ cells in the presence of CpG with or without a transwell insert. After 24 hours, supernatant IFN-γ level was determined by cytometric bead array. Additionally, α-GalCer –loaded liver and spleen pDC were stimulated with CpG and cultured with spleen NK1.1+ cells in the presence of CpG. IFN-γ production was measured after 24 hours. Results: Flt3L-expanded liver pDC stimulated with CpG induced significantly higher CD69 expression on NK cells when compared to spleen pDC. CD69 expression by both groups was reduced by the presence of a transwell insert. Both liver and spleen pDC loaded with α-GalCer and stimulated with CpG induced large amounts of IFN-γ secretion by NK cells. Conclusion: Upon expansion and stimulation, liver pDC are able to stimulate NK cells in vitro. This is partially mediated through cell-cell contact. This work was supported by grant DK068346