The role of antiviral CD8+ T cells in cognitive impairment

https://doi.org/10.1016/j.conb.2022.102603Get rights and content
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Highlights

  • Increased CD8+ T cells is associated with cognitive impairment and Alzheimer's disease.

  • Viral infections promote CD8+ T cell entry into the brain.

  • CD8+ T cells persist in the brain long-term as tissue resident memory cells (TRM).

  • CD8+ T cells and TRM can damage neurons and activate local glial cells.

  • CD8+ T cells and TRM may contribute to cognitive decline following viral infection.

Abstract

The impact of the immune system on the etiopathogenesis of neurodegenerative diseases, including Alzheimer's disease, is a rapidly growing area of investigation. Evidence from human patients and animal models implicates neurotropic viral infections, and specifically the antiviral immune response of brain-infiltrating CD8+ T cells, as potential drivers of disease pathology. While infiltration and retention of CD8+ T cells within the brain following viral infection is associated with improved survival, CD8+ T cells also contribute to neuronal death and gliosis which underlie cognitive impairment in several disease models. Here we review the role of antiviral CD8+ T cells as potential mediators of cognitive impairment and highlight the mechanisms by which brain-resident CD8+ T cells may contribute to neurodegenerative disease pathology.

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