Nature Immunology, Published online: 25 June 2025; doi:10.1038/s41590-025-02209-4

We identify a clonally expanded subset of granzyme K-expressing CD8+ T cells that establish residency in the central nervous system, where they target microglia and help to control the spread of pathogenic phosphorylated tau (pTau) — a hallmark of Alzheimer’s disease and other tauopathies. This CD8+ T cell subset is also found in human brains with pTau lesions.



Summary

A Nature Immunology study identifies a unique population of cytotoxic CD8+ T cells expressing granzyme K within the central nervous system (CNS). These clonally expanded T cells specifically target microglia, limiting the spread of pathogenic phosphorylated tau (pTau), a key feature of Alzheimer’s disease and related tauopathies. Notably, similar CD8+ T cells were also observed in human brains exhibiting pTau lesions, suggesting a conserved mechanism. This discovery highlights the potential therapeutic role of these T cells in controlling neurodegenerative diseases characterized by tau pathology.

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