Plasmacytoid Dendritic Cell-Derived IFN-α Induces TNF-Related Apoptosis-Inducing Ligand/Apo-2L-Mediated Antitumor Activity by Human Monocytes Following CpG Oligodeoxynucleotide Stimulation

摘要: Immunostimulatory oligodeoxynucleotides (ODN) containing the CpG motif are being tested as immune adjuvants in many disease settings. Of human PBMC examined, plasmacytoid dendritic cells (pDC) a major source of type I IFN upon stimulation with ODN. IFNs have numerous immunostimulatory effects, including induction TNF-related apoptosis-inducing ligand (TRAIL)/Apo-2L on monocytes, NK cells, and T cells. Importantly, has also been linked to antitumor responses. Thus, we whether ODN led TRAIL/Apo-2L-induced tumor cell death. When were stimulated ODN, TRAIL/Apo-2L-dependent death was observed. Further examination ODN-stimulated revealed that TRAIL/Apo-2L expression limited CD14(+) which, when depleted, loss TRAIL/Apo-2L-mediated killing. Moreover, pDC depletion abolished killing targets. Analysis showed IFN-alpha production after stimulation. Finally, inclusion neutralizing antiserum during abrogated These results define mechanism by which induces PBMC, ODN-activated produce stimulates express functional TRAIL/Apo-2L.