| Project/Area Number |
12670529
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Aichi Medical University |
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Principal Investigator |
KAKUMU Shinichi Aichi Medical University School of Medicine, Department of Internal Medicine, Lecturer, 医学部, 講師 (10288508)
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| Co-Investigator(Kenkyū-buntansha) |
各務 伸一 愛知医科大学, 医学部, 教授 (10115545)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | host immune response / cytotoxic T lymphocyte / costimulatory molecule / transgenic mouse / DNA immunization / downregulation / B型肝炎ウイルス / 慢性肝炎 / concanavalin A / Propionibacterium acnes |
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| Research Abstract |
The mechanism of chtonicity in viral hepatitis is not well understood until present. Since hepatitis B virus (HBV) and hepatitis C virus (HCV) are not cytopathic, hepatic injury in HBV and HCV infection is thought to be caused by the attack of host immune responses against virus-infected hepatocytes. And it is vaguely thought that the weakness of the immune responses against viral proteins is responsible for the chronicity of viral hepatitis. To elucidate the mechanism of the chronicity, the functions of the cytotoxic T lymphocyte (CIL), one of the main effectors of host immune responses is studied in vitro. The functions of CIL, both proliferative activity and the killing activity were greatly impaired after antigen stimulation without the existence of costimulatory signals. This implies that the hepatocytes lacking the expression of costimulatory molecules may inactivate the CILs after contact and that it may be one of the main mechanisms for the persistence of hepatitis viruses. HBV-transgenic mice (Tg) are the models for HBV carriers in human. Immunization of HBV-Tg with HBs-cDNA results in the downregulation of the virus to some extent, however, the occurrence of complete clearance of viral products is very rare. To increase the efficacy of viral downregulation , cDNAs of HBs and costimulatory molecules (B7 1, B7-2, or CD40) were simultaneously used to immunize HBV-Tg. Although co-immunization with both molecules did not increase the ratio of complete viral downregulation in HBV-Tg, it resulted in the manifestation of hepatitis that was not observed in the immunization of HBs-cDNA alone. This suggests that the efficacy of inducing HBV-specific immune response is improved by the co-immunization. Simultaneous use of costimulatory molecules for immunization may be the clue for the thrapeutic approach to treat chronic infection of hepatitis viruses.
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