| Project/Area Number |
11557048
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
SEKO Yoshinori University of Tokyo, Faculty of Medicine Assistant., 医学部・附属病院, 助手 (30240708)
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| Co-Investigator(Kenkyū-buntansha) |
MISAKI Yoshikata University of Tokyo, Faculty of Medicine Lecturer., 医学部・附属病院, 講師 (60219615)
YAMAMOTO Kazuhiko University of Tokyo, Faculty of Medicine Professor., 医学部・附属病院, 教授 (80191394)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥10,800,000 (Direct Cost: ¥10,800,000)
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| Keywords | myocarditis / dilated cardiomyopathy / Takayasu Arteritis / immunotherapy / T-cell receptor / costimulatory molecule / TNF receptor / ligand superfamily / dilated cardimyopathy / arteritis / cell-mediated immunity / auto-antigen |
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| Research Abstract |
1. Analysis of T-cell receptor(TCR)clonality of the heart infiltrating cells in myocarditis and dilated cardiomyopathy(DCM) : SSCP showed that TCR Vβ clonality was oligoclonal and about 40% of the total clones were identical among different three parts in the same heart and that about 40% of such clones also expanded in the peripheral blood. This indicates a possibility of identification of the antigen recognized by pathogenic T-cell clones playing a primary role in the development of the disease by collecting them from peripheral blood. 2. Analysis of costimulatory molecules playing an important role in the T-cell-mediated myocardial damage in acute and chronic myocarditis : (A)We analyzed TNF receptor/ligand superfamily costimulatory molecules in murine acute myocarditis, and found that CD30L, 4-1BBL, Fas were induced on cardiac myocytes and in vivo anti-4-1BBL or -FasL mAb administration significantly reduced the myocardial damage, indicating the critical role of 4-1BB/4-1BBL and Fa
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s/FasL pathways involved. (B)We found the induction of CD27L, CD30L, OX40L, and 4-1BBL on cardiac myocytes and expression of their counterpart by the infiltrating cells in patients with acute myocarditis and DCM, suggesting the role of these costimulatory molecules in the pathogenesis is of human myocarditis as well. 3. Analysis of TCR clonality of the arterial infiltrating cells in Takayasu Arteritis : (A)SSCP showed that TCR Vβ clonality was oligoclonal and most of the clones were identical between different two parts in the same arterial tissue, suggesting that limited clones infiltrated and recognized a certain antigen and caused vascular damage. (B)TCR γδ repertoire of the infiltrating cells was oligoclonal as was TCR αβ. 4. Analysis of costimulatory molecules in Takayasu Arteritis : It is strongly suggested that among TNF receptor/ligand superfamily costimulatory molecules, especially 4-1BB/4-1BBL and Fas/FasL pathways play an important role in the vascular damage involved in Takayasu Arteritis. Less
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