GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311230/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311230GEOGSEfalseCD8+ T cells are primed by cDC1 and exacerbate tau-mediated neurodegenerationThere 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 cells4,5. We demonstrate that tauopathy mice deficient in cDC1 or cross-presentation 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 secondary lymphoid tissues to prime CD8+ T cells. Our study identifies cDC1 cells as critical for CD8+ T cell priming outside the CNS. This priming is required for a large increase of activated CD8+ T cells in the brain which promotes tau-mediated neurodegeneration.2026/06/30GSE311230GSM9321738GSM9321739GSM9321736GSM9321737GSM9321741GSM9321742GSM9321740GSM9321745GSM9321734GSM9321735GSM9321746GSM9321743GSM9321733GSM932174434328311230Mus musculus