CD8+ T cells exacerbate AD-like symptoms in mouse model of amyloidosis

Xin Wang, Britney Campbell, Monica Bodogai, Ross A. McDevitt, Anton Patrikeev, Fedor Gusev, Emeline Ragonnaud, Konda Kumaraswami, Sophie Shirenova, Karin Vardy, Mohamed Gabriel Alameh, Drew Weissman, Hellen Ishikawa-Ankerhold, Eitan Okun, Evgeny Rogaev, Arya Biragyn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Alzheimer's disease (AD) is linked to toxic Aβ plaques in the brain and activation of innate responses. Recent findings however suggest that the disease may also depend on the adaptive immunity, as B cells exacerbate and CD8+ T cells limit AD-like pathology in mouse models of amyloidosis. Here, by artificially blocking or augmenting CD8+ T cells in the brain of 5xFAD mice, we provide evidence that AD-like pathology is promoted by pathogenic, proinflammatory cytokines and exhaustion markers expressing CXCR6+ CD39+CD73+/- CD8+ TRM-like cells. The CD8+ T cells appear to act by targeting disease associated microglia (DAM), as we find them in tight complexes with microglia around Aβ plaques in the brain of mice and humans with AD. We also report that these CD8+ T cells are induced by B cells in the periphery, further underscoring the pathogenic importance of the adaptive immunity in AD. We propose that CD8+ T cells and B cells should be considered as therapeutic targets for control of AD, as their ablation at the onset of AD is sufficient to decrease CD8+ T cells in the brain and block the amyloidosis-linked neurodegeneration.

Original languageEnglish
Pages (from-to)444-455
Number of pages12
JournalBrain, Behavior, and Immunity
Volume122
DOIs
StatePublished - Nov 2024

Bibliographical note

Publisher Copyright:
© 2024

Keywords

  • Alzheimer's disease
  • Amyloidosis
  • Aβ response
  • B cells
  • CD8 T cells

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