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

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. Overall design: Single cells were prepared from brains pooled from each strain of mice. Cells were stained with propidium iodide, CD45, and CD11b antibodies to identify live CD45hi cells. These cells were sorted by flow cytometer in DPBS supplemented with 20% FBS and the fresh cells were submitted to for single cell sequencing librabry preparation and sequencing