| Project/Area Number |
17590672
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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 | Jichi Medical University |
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Principal Investigator |
KITA Hiroto Jichi medical University, Dept.of Gastroenterology, Assistant professor, 医学部, 助手 (80294974)
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| Co-Investigator(Kenkyū-buntansha) |
SODA Norio Jichi medical University, Dept.of Gastroenterology, Associate professor, 医学部, 講師 (30275680)
UENO Yoshiyuki Tohoku University, Dept.of Gastroenterology, Associate professor, 医学部, 講師 (70282126)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Primary Biliary Cirrhosis / autoimmne / chronic liver disease / autoantibody / autoreactive T cells / immunoregulation / cell therapy / liver immunology / 難治性肝疾患 / 治療 / 細胞性免疫 |
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| Research Abstract |
The aim of this study was to elucidate the pathogenesis of PBC and to develop a new therapy for PBC by analyzing cellular immune response in PBC. Specifically, we have tried to address whether the natural course of PBC can be modified by regulating autoreactive T cells. The major mitochondrial antigens recognized by AMAs have been defined as the E2 components of pyruvate dehydrogenase complexes (PDC-E2). We have already identified PDC-E2 specific CD8 positive autoreactive T cells in both peripheral blood and liver in patients with PBC. The key issue that has remained unsolved is the mechanisms that how these CD8 positive autoreactive T cells are activated and proliferated in vivo. In Heisei 17 nenndo, we have analyzed PDC-E2 specific CD8 positive autoreactive T cell response in AMA negative PBC in order to clarify whether PDC-E2 specific CD8 positive autoreactive T cells are activated in AMA negative PBC. We have demonstrated that PDC-E2 specific CD8 positive autoreactive T cell response was induced in AMA negative PBC patients. These results suggest that abnormal T cell response to self antigen are also associated with disease progression even in AMA negative PBC patients. Thus, autoreactive CD8 T cell responses are in common between AMA positive and negative PBC. Therefore, the regulation of these autoreactive T cells can lead to a new therapy of controlling disease progression. In heisei 18 nenndo, We have further analyzed PDC-E2 specific CD8 positive autoreactive T cell response in AMA negative PBC. We have demonstrated that CD8 positive autoreactive T cell response was identified from about half of the patients with AMA negative PBC. We have also compared CD8 positive autoreactive T cell responses with several clinical parameters. We will further plan to analyze CD4 positive autoreactive T cell response in addition to the CD8 positive autoreactive T cell response
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