Animal study demonstrates that peripheral dendritic cells prime cytotoxic T cells to drive neurodegeneration in tauopathy mice, indicating a systemic immune target for tau pathology.
Key Points
Determine how peripheral CD8+ T cells become activated and primed to infiltrate the brain and accelerate tau-mediated neurodegeneration.
Examined mouse models of tauopathy genetically deficient in conventional type 1 dendritic cells (cDC1s) or defective in antigen cross-presentation.
Assessed neurodegeneration, glial activation, brain infiltration and clonal expansion of CD8+ T cells, and antigen presentation within secondary lymphoid tissues.
Tauopathy mice lacking cDC1s or antigen cross-presentation showed marked protection against neurodegeneration, accompanied by reduced glial activation.
Brain infiltration and clonal expansion of CD8+ T cells were significantly curtailed in dendritic cell-deficient tauopathy mice, while brain-derived antigens were detected in secondary lymphoid organs.