Pathological roles of brain-infiltrating T cells at an early stage of Alzheimer's disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15473
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Keio University
• Principal Investigator: Ohyagi Masaki 慶應義塾大学, 医学部(信濃町), 特任助教 (70882497)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経免疫 / 神経炎症

Outline of Final Research Achievements

Growing evidence has suggested a critical role for neuroinflammation and immune dysfunction in Alzheimer's disease (AD). In addition to microglia, the innate immune cells in the brain, adaptive immune cells also face phenotypic alternation on AD progression. In this study using a mouse mode of AD, we demonstrated that clonally expanded CD8 T cells exhibit protective functions at an early stage of amyloid pathology; however, they inhibit amyloid plaque accumulation in the late phase of AD progression. Single-cell transcriptomic analysis revealed that brain CD8 T cells modify disease-associated microglia phenotypes through chemokine-signaling pathways, and impact amyloid pathology dependent on T cell receptor clonotypes.

Free Research Field

神経免疫

Academic Significance and Societal Importance of the Research Achievements

近年、AD患者脳や脳脊髄液中でオリゴクローナルに増殖するCD8陽性T細胞が着目されているが、その病理学的意義についてはアミロイド病理に促進的あるいは抑制的いずれの報告もあり定まっていない。本研究により、アミロイド病態の病期に応じて脳浸潤CD8陽性T細胞は多様な作用を発揮し、アミロイド病理の進行に関与していることが明らかとなった。今後CD8陽性T細胞の機能修飾によるADの疾患修飾治療を検討する際には、患者の病期に応じた個別化治療戦略が必要と考えられる。