| Project/Area Number |
15K10224
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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 |
Cardiovascular surgery
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内山 雅照 帝京大学, 医学部, 助教 (60713295)
飯田 充 帝京大学, 医学部, 准教授 (20386022)
松山 重文 帝京大学, 医学部, 講師 (90713420)
尾澤 直美 帝京大学, 医学部, 助教 (60713435)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | BTLA / PD-1 / 心臓移植 / マウス / 制御性T細胞 / 冠動脈 / 冠動脈内膜肥厚 / ドナー特異的抗体 / 拒絶反応 |
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| Outline of Final Research Achievements |
In this study, we investigated the effect of anti-PD (programmed death)-1 monoclonal antibody (mAb) and anti-BTLA (B and T lymphocyte attenuator) mAb in fully MHC-mismatched murine model of cardiac allograft transplantation. CBA mice underwent transplantation of C57BL/6 hearts and received one dose of combination of 6B2 and PIM-2 on day 0. Adoptive transfer was performed to determine whether regulatory cells were generated. Cell-proliferation and cytokine assessments were also performed. When CBA mice were given with combination for one dose of 6B2 and PIM-2, the allograft survival was indefinitely prolonged (MST, >100 days). Secondary CBA recipients given whole splenocytes from primary combination-treated CBA recipients with C57BL/6 cardiac allografts 30 days after grafting had prolonged C57BL/6 allograft survival. In conclusion, combination of anti-BTLA mAb and anti-PD-1 mAb could induce indefinite survival of cardiac allografts and may generate regulatory cells.
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| Academic Significance and Societal Importance of the Research Achievements |
抗BTLA抗体と抗PD-1抗体の併用による①各抗体の単独投与よりも強い生着延長効果、②制御性T細胞の誘導による拒絶反応の制御を証明することは、非特異的な免疫抑制剤の減量と慢性拒絶反応制御の解明に繋がり、現代移植医療にとって望ましい結果をもたらす。
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