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2001 Fiscal Year Final Research Report Summary

Analysis of cellular immune responses in perihperal blood and liver tissues in HCV infection

Research Project

Project/Area Number 11470136
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionJichi Medical School

Principal Investigator

IMAWARI Michio  Jichi Medical School, Departmet of Medicine, Professor, 医学部, 教授 (70134228)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Ikuo  Jichi Medical School, Department of Medicine, Lecturer, 医学部, 講師 (40251243)
Project Period (FY) 1999 – 2001
Keywordshepatitis C virus / immunology / helper T cell / cytotoxic T lymphocyte / interferon-γ / interleukin-4 / interleukin-10 / ELISpot
Research Abstract

Hepatitis C virus (HCV) infection frequently persists, progresses to chronic hepatitis and cirrhosis, and finally develops hepatocellular carcinoma. Although viruses in the infected cells are eliminated by virus-specific cytotoxic T lymphocytes (CTLs) that recognize endogenously synthesized, processed viral proteins presented by HLA and lyse the cells, the CTL responses are regulated by helper T cells and immunomodulatory cytokines. In the present study, we investigated mainly the helper T cell and immunomodulatory cytokine responses in peripheral blood ant liver tissues of patients with chronic HCV infection. In chronic HCV infection, type 1 helper T cell responses that produced interferon-γin response to HCV proteins dominated type 2 helper T cell responses that produced interleukin-4. However, HCV proteins stimulated the production of immunosuppressive interleukin-10. In the peripheral blood of patients with chronic hepatitis C, the number of HCV-stimulated interleukin-10-producing cells was larger than that of HCV-stimulated interferon-γ-producing cells. Thus, the anti-HCV responses seemed to be suppressed in the peripheral blood. HCV-specific helper T cells were concentrated in the liver tissues. The number of HCV-stimulated interferon-γ-producing cells in the peripheral blood was inversely correlated with serum HCV RNA levels. Interferon treatment decreased the number of peripheral blood HCV-stimulated interferon-γ-producing cells at 3 month, but the number returned to the pretreatment level later. There were regions in HCV proteins that stimulated of production of interferon-γ and interleukin-10 by peripheral blood mononuclear cells of patients with chronic HCV infection in common. Finally we identified an epitope in HCV recognized by CTLs in association with HLA-A^*0206.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Imawari M: "Pathogenesis of viral hepatitis"Asian Medical Journal. 42. 178-183 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井廻道夫: "ウイルス性肝炎の病態解明の進歩 免疫学的機序の最新知見"内科. 84. 235-239 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura I: "Cellular immune response in HCV Infection"Journal of Gastroenterology. 35. 881-889 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井廻道夫: "ウイルス肝炎の肝障害機序"肝臓. 42. 175-184 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中村郁夫: "HCV感染と細胞性免疫応答"肝胆膵. 43. 617-624 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井廻道夫: "C型肝炎ウイルス"アイピーシー. 282 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imawari M.: "Pathogenesis of viral hepatitis"Asian Medical Journal. 42. 178-183 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura I.: "Cellular immune response in HCV infection"Journal of Gastroenterology. 35. 881-889 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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