Priming of CD8(+) T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration.

In tauopathy mice, absence of cDC1s or antigen cross-presentation protects against neurodegeneration, with reduced brain CD8+ T cell infiltration and glial activation.

• Why it matters: Brain CD8+ T cells correlate with tau pathology severity, but the mechanism by which peripheral T cells are primed to enter the brain and worsen tau-driven damage is unclear.
• What they did: The study used tauopathy mouse models lacking cDC1s or antigen cross-presentation, then assessed brain CD8+ T cell infiltration, clonal expansion, and glial activation; it also tracked presentation of brain-derived antigens in secondary lymphoid tissues.
• The result: cDC1-dependent peripheral priming is linked to CD8+ T cell accumulation in the brain and tau-mediated neurodegeneration, implying impaired priming limits effector expansion.

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