2004 Fiscal Year Final Research Report Summary
Pathogenesis of viral hepatitis based on intrahepatic immune response to hepatitis virus
| Project/Area Number |
15590692
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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 | The University of Tokyo (2004)
Tokyo Medical University (2003) |
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Principal Investigator |
KAKIMI Kazuhiro The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 寄附講座教員(客員助教授) (80273358)
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| Co-Investigator(Kenkyū-buntansha) |
ITOI Takao Tokyo Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (60338796)
MATSUSHIMA Kouji The University of Tokyo, Graduate School of Medical Science, Professor, 大学院・医学系研究科, 教授 (50222427)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hepatitis virus / HBV / CTL / chemokine / cytokine |
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| Research Abstract |
The distribution and dynamics of the cytotoxic T lymphocyte (CTL) response to hepatitis B surface antigen (HBsAg) were studied in mice after intramuscular DNA immunization and after hepatic infection by a recombinant adenovirus that expresses the hepatitis B virus genome (Ad-HBV). CTLs specific for HBsAg accumulate preferentially in the spleen after DNA immunization but are primarily intrahepatic after Ad-HBV infection. The secondary CTL response to Ad-HBV in DNA-primed mice is characterized by rapid depletion of effector CTLs from the spleen, and their expansion in the liver where they cause hepatitis, secrete interferon gamma (IFNγ), and inhibit HBV gene expression. Together with intrahepatic IFNγ expression, CXCL9 and CXCL10 mRNAs were strongly induced in the liver. Suppression of HBsAg synthesis is accompanied by disappearance of intrahepatic IFNγ-producing CTLs and their reaccumulation in the spleen. The data suggest a possible explanation for the paucity and functional deficiency of HBV-specific CTLs in the periphery during chronic HBV infection, and that the severity of infection can be worsened by a preexisting CTL response if neutralizing antibody is not also present.
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