| Project/Area Number |
14370190
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Showa University (2003-2004)
Jichi Medical University (2002) |
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Principal Investigator |
IMAWARI Michio Showa University, School of Medicine, Professor, 医学部, 教授 (70134228)
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| Co-Investigator(Kenkyū-buntansha) |
HIROISHI Kazumasa Showa University, School of Medicine, Assistant professor, 医学部, 講師 (80296996)
ITO Takayoshi Showa University, School of Medicine, Associate, 医学部, 助手 (50317517)
NAKAMURA Ikuo Jichi Medical School, Faculty of Medicine, Assistant professor (40251243)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | hepatitis C virus / cytotoxic T cell / interferon / epitope / HLA-A24 |
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| Research Abstract |
Hepatitis C virus (HCV) infection frequently persists, and leads to chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Acute HCV infection has decreased dramatically after universal use of disposable medical instruments and introduction of HCV test for blood products. Elimination of HCV from chronic hepatitis C patients became possible by interferon therapies. However there are still many patients who do not respond to the therapy. Since cytotoxic T lymphocytes (CTL) play an important role in elimination of infected viruses, the therapy that augments HCV-specific CTL responses may be effective for such patients. We developed the system that assesses CTL responses of peripheral blood to whole HCV antigens. Using the system, we found that HCV-specific CTL responses of patients treated with interferon decreased in accord with the decrease of HCV in serum, and that a temporary interruption of the therapy augmented CTL responses by stimulation with re-appeared HCV. We also attempted to identify HCV-specific CTL epitopes as many as possible for future development of HCV peptide vaccines. Using HCV peptides with HLA-A24-binding motif or overlapping peptides encompassing the whole HCV protein, we identified 16 novel HCV-specific CTL epitopes by interferon-', ELISpot assay. We also analyzed the phenotypes of HCV-specific CTL using CTL epitope peptide-HLA-A24-Ig dimers and cell surface markers, and found that HCV-specific CTL in the peripheral blood were poorly activated and differentiated variously.
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