CD8T cells exacerbate AD-like symptoms in mouse model of amyloidosis.

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 CD8T cells limit AD-like pathology in mouse models of amyloidosis. Here, by artificially blocking or augmenting CD8T cells in the brain of 5xFAD mice, we provide evidence that AD-like pathology is promoted by pathogenic, proinflammatory cytokines and exhaustion markers expressing CXCR6CD39CD73CD8T-like cells. The CD8T 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 CD8T cells are induced by B cells in the periphery, further underscoring the pathogenic importance of the adaptive immunity in AD. We propose that CD8T 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 CD8T cells in the brain and block the amyloidosis-linked neurodegeneration.