title: Induction of hepatic injury by hepatitis C virus-specific CD8+ murine cytotoxic T lymphocytes in transgenic mice expressing the viral structural genes.
abstract: In the present study, we generated killer cells specific for hepatitis C virus (HCV) structural protein by re-stimulation of immune spleen cells from H-2(d) haplotype transgenic (Tg) mice, expressing the core, E1, E2, and NS2 genes of HCV regulated by the Cre/loxP switching system. The generated killer cells were conventional CD8(+)L(d) class-I MHC molecule-restricted cytotoxic T lymphocytes (CTLs) and specific for the HCV E1 structural protein. Because the CTLs could also kill hepatocytes from the Tg mice expressing HCV structural proteins in vitro, we attempted to transfer those CTLs intravenously into interferon regulatory factor-1 (IRF-1) negative, CD8-deficient Tg mice representing the HCV structural genes on hepatocytes to examine whether the inoculated CD8(+) CTLs can eliminate hepatocytes expressing the HCV genes in vivo. We observed an elevation of serum ALT level as well as damage of the liver tissue histologically. To our knowledge, this is the first demonstration to show that HCV-specific CD8(+) CTLs specifically attack hepatocytes expressing the HCV structural proteins both in vitro and in vivo.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical, School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Takaku
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Norose
authors.forename: Isao
authors.initials: I
authors.lastname: Maruyama
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Teruo
authors.initials: T
authors.lastname: Takano
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D005814:Genes, Viral; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019076:Transgenes; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D014764:Viral Proteins; D015678:Viral Structural Proteins; C045073:Cre recombinase; D019426:Integrases