Graft protective effect and induction of CD4+CD25+Foxp3+ T cell by combination of anti-BTLA mAb and anti-PD-1 mAb
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 |
Section | 一般 |
Research Field |
Cardiovascular surgery
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Research Institution | Teikyo University |
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 |
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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Report
(5 results)
Research Products
(21 results)
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[Journal Article] Seven Japanese Herbals Prolonged Cardiac Allograft Survival.2018
Author(s)
Enzhi Yin, Xiangyuan Jin, Masateru Uchiyama, Qi Zhang, Takako Yanagisawa, Akira Inoue, Yu Guo, Masanori Hara, Shigefumi Matsuyama, Tomohiro Imazuru, Masafumi Kawamura, and Masanori Niimi
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Journal Title
Transplantation Proceedings
Volume: 印刷中
Issue: 9
Pages: 2789-93
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Anti-CD272 antibody (6B2) induced prolongation of fully MHC-mismatched murine cardiac allograft and generation of Foxp3+ regulatory T cells.2017
Author(s)
Masateru Uchiyama, Xiangyuan Jin, Enzhi Yin, Takako Yanagisawa, Akira Inoue, Masanori Hara, Shigefumi Matsuyama, Tomohiro Imazuru, Hideo Yagita, Masafumi Kawamura, and Masanori Niimi
Organizer
アジア移植学会2017
Place of Presentation
フィリピン・セブ
Year and Date
2017-11-27
Related Report
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