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Induction of hepatic injury by hepatitis C virus-specific CD8+ murine cytotoxic T lymphocytes in transgenic mice expressing the viral structural genes
- Source :
- Biochemical and biophysical research communications. 301(2)
- Publication Year :
- 2003
-
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.
- Subjects :
- Cytotoxicity, Immunologic
Genes, Viral
Hepatitis C virus
Transgene
Biophysics
chemical and pharmacologic phenomena
Mice, Transgenic
Hepacivirus
Biology
CD8-Positive T-Lymphocytes
Major histocompatibility complex
medicine.disease_cause
Biochemistry
Adenoviridae
Cell Line
Mice
Viral Proteins
Immune system
Interferon
medicine
Cytotoxic T cell
Animals
Transgenes
Molecular Biology
Viral Structural Proteins
Mice, Inbred BALB C
Integrases
Structural gene
virus diseases
Cell Biology
Virology
Molecular biology
digestive system diseases
Liver
biology.protein
Hepatocytes
Female
CD8
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 301
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....697d01453ae16578fab0b23a73657a76