Development of novel approach targeting on the specific molecule of memory lymphocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K22646
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Ueki Shinya 北海道大学, 医学研究院, 客員研究員 (30837258)
• Co-Investigator(Kenkyū-buntansha): 後藤 了一 北海道大学, 大学病院, 講師 (10645287) ; 財津 雅昭 北海道大学, 医学研究院, 客員研究員 (20768981) ; 渡辺 正明 北海道大学, 医学研究院, 特任講師 (40789848)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 記憶T細胞 / 免疫寛容

Outline of Final Research Achievements

To identify the therapeutic target molecules in the resistance of transplant tolerance in sensitized mouse model, we used delayed anti CD3 antibody for sensitized mice in heart transplant model. Sensitized mice treated with delayed anti-CD3 antibodies, promoted an allograft rejection rapidly. We found that TCF1low PD-1+ CD8+ T cells played a crucial role for graft rejection in sensitized model. Further, TCF1high PD-1+ CD8+ T cells were key for tolerance induction. We reported these findings in ‘Immunohorizens’ in 2024. Unfortunately, we could not find any effect of inhibitor of inflammasome which is one of the key molecules in the signaling pathway of P2X7 receptor. The inhibitor of inflammasome together with another immunosuppressants may be of interest in the future.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

臓器移植後は終生の免疫抑制剤の内服が必要で、それに伴う腎不全、代謝異常、悪性腫瘍発生などが問題である。免疫寛容は免疫抑制剤の使用無しで拒絶反応が生じない状態であり、その誘導は臓器移植の最終目標とされるが、ヒトでは記憶T細胞が免疫寛容の障壁となり達成できていない。本検討で明らかにした記憶T細胞の治療ターゲット分子は拒絶反応を引き起こすT細胞を特異的に抑制する一方で、免疫寛容誘導に重要なT細胞の温存が可能で、臓器移植医療における革新的な治療法につながる可能性がある。