Graft protective effect and induction of CD4+CD25+Foxp3+ T cell by combination of anti-BTLA mAb and anti-PD-1 mAb

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10224
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Teikyo University
• Principal Investigator: Imazuru Tomohiro 帝京大学, 医学部, 准教授 (40359576)
• 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)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: BTLA / PD-1 / 心臓移植 / マウス / 制御性T細胞

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.

Free Research Field

心臓血管外科学

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。