The allo-reactivity of graft infiltrating lymphocytes during early timing post-transplantation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18047
• 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: Hokkaido University
• Principal Investigator: Zaitsu Masaaki 北海道大学, 医学研究院, 客員研究員 (20768981)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: グラフト浸潤細胞 / 免疫不全マウス / アロ攻撃性 / 心移植

Outline of Final Research Achievements

To identify immunological behaviors of graft infiltrating lymphocytes (GILs) during early post-transplantation (Tx), the alloreactivity of GILs using a murine model of cardiac Tx was assessed. GILs from 120 hours (h) allografts, but not 72 h allografts, showed robust activation and produced proinflammatory cytokines. BALB/c Rag2-/-γc-/- (BRG) mice reconstituted with 120 h GILs displayed donor-specific immune reactivity and rejected donor strain cardiac allografts. Conversely, 72 h GILs exhibited weak anti-donor reactivity and did not reject allografts. These findings were confirmed by re-Tx of cardiac allografts into BRG mice at 72 h post-Tx. Re-transplanted allografts continued to function for >100 days, despite the presence of allogeneic CD3+ GILs. The immunological behavior of GILs considerably differs over time during the early post-Tx phase. Newly infiltration of GILs after 72 h post-Tx may play a critical role for graft rejection.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

臓器移植では移植直後から終生にわたり免疫抑制剤が必要であり、薬剤の副作用（腎障害、易感染性、悪性腫瘍の発生など）が問題である。効率的、特異的な免疫抑制が必要だが、アロ抗原特異性を獲得する時期、特異的な攻撃細胞を同定するマーカーなど分かっていない。本研究で明らかにしたアロ攻撃性細胞の移入時期の同定は、特異的な免疫抑制療法や免疫抑制剤の軽減に有用である。また、微小環境に移入した細胞の機能を測定することで、抗原特異的な細胞の同定、更には最近注目されている癌微小環境の機序解析に有用な解析ツールの提供にもつながる可能性がある。