New therapeutic vaccines by using small membrane vesicle secreted by dendritic cells: New development for chronic virus infections

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In this study, we investigated whether exosome (Ex) derived from dendritic cells (DC) can be attractive candidate for antiviral immunity in the transgenic mice (HHD) expressing HLA-A0201. We isolated Ex from culture supernatant of DC that were infected with recombinant Adenovirus (Rec Ad) expressing NS3-5A of Hepatitis C virus (HCV) with or without maturation reagents of DC such as LPS, IL-12, CpG, phorbor ester, ionomycin, CD40L or ATP. By estimating dot blot assay, Ex contained CD63, CD81, CD44, I-Ab, HLA-A2, HSP, and Raeδ. Responses of cytotoxic T lymphocytes (CTL) or natural killer cells were induced by these Exs. IFN γsyntheses estimated by ELISPOT assay showed increased numbers of secreting cells. From the findings of increased concentration of Raeδand HSP in Exs and the frequency of NKG2D-positive cells in the splenic cells after the Ex stimulation, we hypothesized that NK cell increases in number induce IFN γ synthesis and cytolytic function in part just after the Ex stimulation. CD8+ T cells, but not CD4+ T cells may be important for the effects of Ex on CTL responses. Among the TLRs tested, TLR-2 suggested an important role as receptor of Ex in addition to the well known LFA molecules.