CD8+ T cells are primed by cDC1 and exacerbate tau-mediated neurodegeneration
Hu, H.; Lin, P. B.-c.; Zeng, C.; Sharma, P.; Li, Y.; Jiang, H.; Nulman, J.; Ohara, R. A.; Wu, T.; Li, S.; Yokoyama, W. M.; Artyomov, M.; Murphy, K. M.; Ulrich, J. D.; Holtzman, D.
Show abstract
There are changes in adaptive immunity in Alzheimers disease (AD) and increases in activated CD8+ T cells in brain correlate with tau pathology1-3. 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 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.
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