1998 Fiscal Year Final Research Report Summary
Molecular and immunological study on the pathogenesis of hepatitis C
| Project/Area Number |
07407015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Jichi Medical School |
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Principal Investigator |
IMAWARI Michio Jichi Medical School, Department of Medicine, Professor, 医学部, 教授 (70134228)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Takashi Jichi Medical School, Department of Medicine, Associate, 医学部, 助手 (10254913)
MORIYAMA Takashi Jichi Medical School, Department of Medicine, Instructor, 医学部, 講師 (10240706)
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| Project Period (FY) |
1995 – 1998
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| Keywords | hepatitis C / hepatitis C virus / cytotoxic T lymphocyte / HLA B44 / epitope / perforin / Fas / TNF |
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| Research Abstract |
In the present study, we demonstrated that HLA B44-positive hepatitis C patients with demonstarable CTL response to HCV core antigen a.a. 88-96 had lower levels of serum HCV RNA, suggesting that CTL may suppress the outgrowth of HCV.In addition, CTh response was observed to multiple HCV epitopes in the same patients. Thus CTL response to HCV infection is not strong enough to eliminate the virus.
The variation of amino acid in HCV core a. a. 88-96 was observed only 3 of 27 HLA B44-positive patients. All three variants could be recognized by CTL as effectively as wild-type HCV antigen, but two of three variants could not induce CTL effectively while the other one could induce CTL.Furthermore, when a small amount of variant HCV co-existed with wild-type HCV, the induction of CTL recognizing spesifically variant epitope was sppressed.
HCV-specific CTL recognized and killed HCV-infected target cells by perform-, Fas ligand-, and. TNF-based mechanisms. In addition, activated CTL killed bystander sensitive non-infected cells by Fas ligand and TNF-based mechanisms. The mechanisms may contribute to the expansion of inflammation in the liver.
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