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CD8 T cells are primed by cDC1 and exacerbate tau-mediated neurodegeneration

GSE279315 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/09/30 Platform GPL34290
Summary
There are changes in adaptive immunity in Alzheimer’s disease (AD) and increases in activated CD8 T cells in brain correlate with tau pathology. However, which cells mediate T cell priming in tau-mediated neurodegeneration remains unclear. In different conditions such as cancer, viral infections, and autoimmune diseases outside the CNS, conventional type-1 dendritic cells (cDC1) perform antigen cross-presentation to prime CD8 T cells. We demonstrate that tauopathy mice deficient in cDC1 are markedly protected against tau-mediated neurodegeneration and display a selective decrease in brain CD8 T cell infiltration and glial reactivity. The remaining CD8 T cells showed an antigen inexperienced status with less clonal expansion, indicating suboptimal T cell priming. We confirm that brain derived antigens are presented in the secondary lymphoid tissues to prime CD8 T cells. Our study identifies cDC1 as critical for CD8 T cell priming outside of the CNS. This priming is required for a large increase in activated CD8 T cells in the brain which promotes tau-mediated neurodegeneration.
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Also filed as BioProject PRJNA1171841 and SRA study SRP537985. Searching any of these in the dataset finder brings you back here.

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