Increased CD8+ T cells is associated with cognitive impairment and Alzheimer's disease.
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Viral infections promote CD8+ T cell entry into the brain.
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CD8+ T cells persist in the brain long-term as tissue resident memory cells (TRM).
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CD8+ T cells and TRM can damage neurons and activate local glial cells.
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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.