| Project/Area Number |
10357005
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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 | 展開研究 |
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| Research Field |
Neurology
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| Research Institution | Tokyo metropolitan Institute for Neuroscience (1999-2000)
Tokyo Metropolitan Institute for Neuroscience (1998) |
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Principal Investigator |
MATSUMOTO Yoh Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所・神経病理研究部門, 参事研究員 (90173921)
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| Co-Investigator(Kenkyū-buntansha) |
KOHYAMA Kuniko Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所・神経病理研究部門, 研究員 (80301795)
TANUMA Naoyuki Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所・神経病理研究部門, 研究員 (00281676)
MATSUBARA Shiro Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所・神経病理研究部門, 研究員 (00143884)
池 映欣 (財)東京都医学研究機構, 東京都神経科学総合研究所・神経病理学研究部門, 客員研究員
JEE Youngheun Tokyo Metropolitan Inst. for Neurosci.
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥32,800,000 (Direct Cost: ¥32,800,000)
Fiscal Year 2000: ¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1999: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1998: ¥16,100,000 (Direct Cost: ¥16,100,000)
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| Keywords | Central nervous system / Autoimmune disease / T cell receptor / CDR3 spectratyping / DNA avaccine |
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| Research Abstract |
In this study, we have modified and applied CDR3 spectratyping analysis which is a sensitive method to detect T cell clonal expansion to identify T cells bearing autoimmune disease-associated T cells (TCR). Based on the results obtained by the analysis, we have made DNA vaccines i.e. expression vectors encoding the Vbeta chain of TCR of encepahlotogenic T cells, and tried to protect animals immunized with neuroantigen plus complete Freund adjuvant from the development of experimental autoimmune encephalomyelitis(EAE). The basic principle of DNA vaccination therapy is as follows. When DNA vaccines are injected in animals, TCR genes are transcribed and translated into TCR oriteubs. Then, these proteins overexpressed in vaccinated animals induce anti-TCR antibodies and/or regulatory T cells, which in tern inhibit the proliferation of encephalitogenic T cells bearing the same TCR.The TCR duagbisus abd DNA vaccination therapy established in animal models will provide useful information to t
… More
he development of TCR analysis and TCR-based immunotherapy in human diseases in the near future.
In EAE induced in Lewiw rats, we found that 1)Vβ8.2 clonal expansion was observed in T cells infiltrating the central nevous system(CNS), 2)this finding was observed not only in the CNS, but also in peripheral blood lymphocyts, enabling the diagnosis of the disease satus using the peripheral blood, and that 3)when the major encephalitogenic T cells bearing Vβ8.2 were depleted with the corresponding antibody, second encephalitogenic T cells bearing Vβ10 were newly activated. These findings suggest that TCR-based immunotherapy should be directed at these T cells simultaneously to obtain sufficient desease suppression.
In our recent studies, we identified autoimmune cardititis-inducing T cells that had been not known by CDR3 spectratyping and seceeded in preventing the disease by injection of the corresponding TCR DNA vaccine(J.Immunol., 2000). However, the effects of vaccines on EAE suppression is not sufficient. By improving the vaccine constructs and determining the most effective protocols for vaccine administration, reliable DNA vaccination should be established. Our final goal is to develop TCR-based immunotherapy for human neurological autoimmune diseases. Less
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