In this setting, anti-viral ISGs, such as indolamine-2, 3-dioxygenase (IDO) or APOBEC3G, were strongly

induced in HBV-Huh7, the degree of which was inversely Vismodegib correlated with HBV quantity. These results indicate that BDCA3+DCs are capable of enhancing NK-mediated, but non-cytolytic HBV suppression via induction of ISGs. CONCLUSIONS: Bystander DCs utilize NK cells to suppress HBV replication in infected hepatocytes. Plasmacytoid DCs enhance cytolytic NK activity, while BDCA3+ DCs stimulate their non-cytolytic capacity of inducing ISGs, showing a proof of concept on immunological HBV control. Disclosures: The following people have nothing to disclose: Sachiyo Yoshio, Tatsuya Kanto, Masaya Sugiyama, Hirotaka Shoji, Yohei Mano, Yoshihiko Aoki, Nao Nishida, Masaaki Korenaga, Kazumoto Murata, Masashi Mizokami Aims: Hepatitis B virus (HBV) infection occasionally causes massive liver damage. Although cytotoxic T lymphocytes (CTLs) play a critical role in hepatitis, the mechanism of massive liver cell damage by HBV infection has not been elucidated sufficiently due to lack of an animal model. In this study, we attempted to establish a hepatitis B animal model using human hepatocyte transplanted NOG mice and human peripheral blood mononuclear cells (PBMCs). Methods: Eight-week-old

TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV) twice a day. Two days after the initial injection, mice were re-injected with the same amount of GCV. Seven days after the first GCV injection, mice were transplanted with human hepatocytes Tanespimycin manufacturer LY294002 obtained from an HLA-A24 donor. Eight weeks after hepatocyte transplantation, mice were injected intravenously with 50 μL of HBV-positive human serum samples. Eight weeks after HBV infection, mice were inoculated with 5 x 106 human PBMCs isolated from an HLA-A24 patient who recovered from acute severe hepatitis B. Two weeks after PBMC injection, liver pathology, mice serum human albumin, which is correlated with the

human hepatocyte repopulation index (ELISA), HBV DNA levels (real-time PCR) and the pheno-type of human PBMC (FACS) were analyzed. Results: Transplantation of human PBMCs resulted in up to 82 %human mononuclear cell chimerism in the liver. Massive hepatocyte damage and decrease in serum human albumin with a decline in HBV DNA levels were seen in HBV-infected mice, but not uninfected and PBMC-transplanted mice. The population of regulatory T cells was significantly lower in HBV-infected mice compared to that of uninfected mice. In HBV-infected mice, HBV-specific CTLs were detected by tetramer. Serum ALT, gran-zyme A and interferon-gamma levels were elevated only in HBV infected and PBMC transplanted mice. Two weeks after injection of human PBMCs, the value of hepatitis B surface (HBs) antigen decreased below the detectable limit, and anti-HBs antibody became positive in all 6 mice. Such a decrease in HBs antigen was not observed in mice with only HBV infection.