Development of novel immune regulating strategy to induce allo-specific exhaustion after transplantation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17553
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Hiroshima University
• Principal Investigator: Tanimine Naoki 広島大学, 病院(医), 助教 (70866516)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 免疫寛容 / 自然免疫寛容 / アロ応答性T細胞 / 免疫モニタリング

Outline of Final Research Achievements

Allo-reactive T cells after organ transplantation is known as key player of post-transplant allo-immune response. The mechanism of regulation for allo-reactive T cells could be central for understanding of tolerance. In this study, focusing on allo-reactive T cells, we developed a novel monitoring method to detect donor-specific immune response for rejection and tolerance in mouse skin transplantation models.
With human samples, we also developed a method for multiplex single cell RNA sequence (scRNA-seq) for analyzing allo-reactive T cells. We successfully generated a series of library for scRNA-seq from recipients after living-donor liver transplantation under stable condition with regular immune suppression and clinical tolerance. They will be expected to open the new mechanism for spontaneous tolerance after liver transplantation.

Free Research Field

移植免疫学

Academic Significance and Societal Importance of the Research Achievements

臓器移植後移植臓器に対するアロ免疫応答を詳細かつ臨床需要を満たす短時間で把握するモニタリング法の確立によって、個別化し免疫抑制療法を提供することを通じて移植医療のさらなるが成績向上が期待される。同時に、本アッセイは基礎研究においても詳細な免疫応答細胞を生細胞として解析可能な新たな解析手法としての有用性を認める。移植後免疫制御機構の解明に大きく寄与することで、新たな免疫抑制良好の開発に向けて応用が期待される。