Analysis of chronic rejection (graft coronary arteriosclerosis) after heart transplantation

• Project/Area Number: 24592069
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Ehime University
• Principal Investigator: IZUTANI Hironori 愛媛大学, 医学(系)研究科(研究院), 教授 (90419200)
• Co-Investigator(Kenkyū-buntansha): RYUGO Masahiro 愛媛大学, 大学院医学系研究科, 講師 (90423459)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 心臓移植 / 慢性拒絶反応 / 冠動脈硬化症 / 移植免疫 / 心移植

Outline of Final Research Achievements

Graft coronary arteriosclerosis occurs as chronic rejection after heart transplantation. It is an unsolved lethal clinical issue for improving heart transplant outcome. However, the mechanism of the disease is still unknown. Using heterotopic rat heart transplantation and a retransplantation model, we whowed that retransplantation of allografts back into the donor strain did not prevent graft arteriosclerosis if the grafts had resided in the primary recipient for up to five days. In the retransplantation model, CD4+ T cells and/or CD8+ T cells, or macrophage of first recipient rats in both combinations were eliminated by monoclonal antibodies, and we found that the administration of both anti-CD4 and anti-CD8 monoclonal antibodys or macrophage depletion reduced graft coronary arteriosclerosis and development. In conclusion, the T cell subsets, CD4+ T cell and CD8+ T cell and/or macrophage play a certain role in the induction of the graft coronary arteriosclerotic change.