| Project/Area Number |
16K08474
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | アロT細胞 / ワクチンベクター / アロ抗体産細胞応答 / 脾臓 / XCR1陽性DC / DST / ハプテン抗原 / FITC抗原 / アロ抗体産生応答 / 免疫組織染色 / XCR1 / FITC / ドナー特異的輸血 / ドナー特異的抗体 / 抗体産生応答 / 細胞増殖 / サイミジンアナログ / フェノタイプ解析 / 細胞間相互作用 / 多重免疫染色 / 免疫学 / 細胞･組織 / DST(ドナー血輸血) / チミジンアナログ |
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| Outline of Final Research Achievements |
Donor-specific blood transfusion (DST) is one of the tolerance-inducing protocols used in not only experimental but also clinical transplantation, but detailed mechanism is unknown. The first, we demonstrated that a single DST efficiently induces a anti-donor class I MHC (MHCI) antibody-forming cell and donor-specific regulatory T cell responses, mainly in the spleen. Therefore, in this study, we examined primarily focused on a nature of these antibodies and a mechanism for this efficient alloresponse in rats. The result, we found the T-cells in the blood transfusion can alloresponse most efficiently in the spleen PALS. In spleen, after killed donor T-cell by NK cells, XCR1+ resident dendritic cells phagocytosed donor MHCI + fragments, induced AFC-response. In addition, Hapten-antigen labeled donor T-cell induced AFC-response and produced anti-FITC antibody. The conclusion, Allogeneic T-cells may be clinically applicable as vaccine vectors for prophylactic antibody production even.
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| Academic Significance and Societal Importance of the Research Achievements |
研究代表者は、輸血液中のドナーT 細胞がドナー特異的輸血（DST） のアロ抗体産生応答（AFC 応答）を最も効率的に誘導することを突き止め、その誘導メカニズムを明らかにした。さらにハプテン抗原を結合させたドナーT 細胞の移入実験によって、脾臓で抗ハプテンAFC 応答が起こることを証明した。これによりウイルスや腫瘍のペプチドをT 細胞に結合させて、効率よく抗ペプチド 抗体を作らせるという全く新しいワクチン構想の提案に繋がるという意義がある。
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