| Project/Area Number |
12670494
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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 | Ehime University |
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Principal Investigator |
AKBAR S.m.f. Ehime University, Faculty of Medicine, Instructor, 医学部, 助手 (90294793)
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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 |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Liver Diseases / Liver dendritic cells / Surface markers / Cytokines / Antigen presentation |
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| Research Abstract |
Dendritic cells (DC) are the most potent professional antigen-presenting cells (APC). DC process and present antigen to naive T cells and also ensure the functioning and survival of activated lymphocytes. Although widely distributed in the body, the phenorype and function of DC differs according to their localization and levels of maturation. We showed that defective function of peripheral blood DC in patients with chronic hepatitis B and activation and maturation of peripheral blood DC during vaccine therapy. We also detected mature DC from the liver tissues from patients with chronic liver diseases and further showed a lack of mature DC at the liver tissue in hepatocellular carcinoma. However, it was not possible to isolate this trace population of APC from the human liver due to technical limitation.
To over come this, we isolated liver DC from normal as well as from a mouse model of hepatitis. Liver DC from normal mouse showed an immature phenotype expressing very low levels of costimulatory molecules like CD40, CD80 and CD86. However, after encountering antigens, liver DC were capable of capturing, processing and presenting soluble antigens to T cells. Next, we checked whether the function of liver DC were compromised during inflammation of the liver. Experimental hepatitis was induced in C57BL/6 by injecting concanavalin A (Con A). Liver DC from mice with hepatitis could not induce proliferation of antigen-specific T cell and immune regulatory cytokines. The findings of impaired function of liver DC from mice with experimental acute hepatitis was further confirmed by studying the function of liver DC in a mouse model of chronic hepatitis.
In summary, these studies indicate that impaired APC capacity of liver DC during hepatitis may underlie the impaired magnitude of antigen-specific immune response during hepatitis.
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