Analysis and therapeutic application of crosstalk between innate immunity and acquired immunity in viral hepatitis.
| Project/Area Number |
17590688
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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 |
ISHIKAWA Tetsuya Aichi Medical University, School of Medicine, Faculty of Medicine, Associate Professor (10288508)
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| Co-Investigator(Kenkyū-buntansha) |
KAKUMU Shinichi Aichi Medical University, School of Medicine, Faculty of Medicine, Professor (10115545)
OKUMURA Akihiko Aichi Medical University, School of Medicine, Faculty of Medicine, Lecturer (70288512)
ITO Hiroyasu Gifu University, Graduate School of Medicine, Lecturer (80373075)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | hepatitis B virus / transgenic mouse / NKT cell / cytotoxic T lymphocyte / α-galactosylceramide / IL-2 / CD40 / CD4OL / サイトカイン |
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| Research Abstract |
Natural killer T (NKT) cells are one of the major cell populations in the liver and thought to play important roles on immune-pathogenesis of hepatitis. On the other hand, cytotoxic T lymphocytes (CTLs) are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus(HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide (α-GalCer), a ligand for Vα14-positive NKT cells stropgly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or α-GalCer alone failed to induce HBsAg-specific CTLs, but co-administration of the both compounds did induce them. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40/CD4OL interaction mediate the enhancement of CTL induction caused by α-GalCer through NKT cell activation. The crosstalk between innate and acquired immunity could be applied to the intractable infectious diseases like HBV infection.
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Report
(3 results)
Research Products
(14 results)
