| Project/Area Number |
09044341
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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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,FIRST DEPARTMENT OF INTERNAL MEDICINE,PROFESSOR, 医学部, 教授 (10115545)
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| Co-Investigator(Kenkyū-buntansha) |
GUIDOTTI L.G. THE SCRIPPS RESEARCH INSTITUTE,DEPARTMENT OF MOLECULAR AND EXPERIMENTAL MEDICINE, Departmen, Assistant
CHISARI F.V. THE SCRIPPS RESEARCH INSTITUTE,DEPARTMENT OF MOLECULAR AND EXPERIMENTAL MEDICINE, Departmen, Professor
ISHIKAWA Tetsuya AICHI MEDICAL UNIVERSITY,FIRST DEPARTMENT OF INTERNAL MEDICINE,ASSISTANT PROFESS, 医学部, 助手 (10288508)
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| Project Period (FY) |
1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | HEPATITIS B VIRUS / TRANSGENIC MOUSE / CYTOTOXIC TLYMPHOCYTE / ANTI-VIRAL EFFECT / ANTI-INFLAMMATORY THERAPY / MUTATED PEPTIDE / ANTAGONIST / VACCINE |
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| Research Abstract |
Hepatitis B virus (HBV) transgenic mouse (TgM) was used to analyze immunopathogenesis of viral hepatitis. Hepatic injury after adoptive transfer of HBsAg-specific cytotoxic Tlymphocytes (CTL) to HBV TgM was monitored by measuring serur ALT levels, and anti-viral effect of CTL was monitored by measuring HBV mRNA remaining in the liver of TgM 5 days after the transfer of CTL.Using CTLs with same specificity but with different TCRs and different cytokine profiles, the effects of individual CTLs on disease severity and viral elimination were anlyzed. Anti-viral effect of CTLs well-0correlated with the amount of cytokines produced by CTLs, like IFN-gamma and TNFalpha, however, the severity of hepatic injury did hot correlate with the amount of those cytokines. These results suggest that the severity of hepatitis and the efficiency of viral clearance are affected by the characteristics of CTLs and taht the factors responsible for each phenomenon (disease and viral clearance) are different. The more detailed study is needed to clarify the factor taht is most responsible for the disease exacerbation of hepatitis and to apply those observation to the anti-inflammatory therapy of hepatitis.
Murine HBsAg-specific CTL clones recognize the peptide that locates the residue 28-39 of HBsAg in association with L^d molecule. In spite of the different TCR bata gene usage, they all recognize the residue 33 as TCR contact site. with the peptides that have mutations at this position, we are now screening the ones that can work as antagonists, or the ones that are more immunogenic than the wild type peptides. We think that those mutated peptides can be utilized to treat severe hepatitis, or to break tolerance of chronically infected patients as vaccine, respectively.
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