CD8+ T lymphocytes in progressive supranuclear palsy and corticobasal degeneration: Interactions with tau pathology and neuroinflammation.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are primary 4R tauopathies characterized by regionally selective accumulation of hyperphosphorylated tau and progressive neurodegeneration. Accumulating evidence suggests that neuroinflammatory and adaptive immune mechanisms contribute to their pathophysiology, although their precise function remains incompletely understood. This narrative review summarizes the involvement of CD8+ T lymphocytes in PSP and CBD, with particular emphasis on their phenotype, spatial distribution, and interactions with glial cells. A comprehensive literature search was conducted to identify relevant human and experimental studies examining central and peripheral immune responses. Existing data indicate that CD8+ T-cell infiltration is a consistent feature of PSP, particularly within vulnerable subcortical and brainstem regions such as the substantia nigra, where these cells are in close association with neurons and activated microglia. Their distribution correlates with phosphorylated tau burden and glial activation markers, consistent with coordinated innate-adaptive immune responses. Emerging evidence further suggests that CD8+ T cells in tauopathies may adopt non-classical phenotypes, including granzyme K-expressing (GZMK+) subsets, which may influence microglial activation rather than exert purely cytotoxic roles. In contrast, evidence in CBD remains limited and is largely derived from broader FTLD-tau cohorts, where CD8+ T cells are predominantly associated with cortical tau pathology and glial activation. Overall, CD8+ T lymphocytes appear to represent a common component of the neuroinflammatory environment in tauopathies, although their functional role remains context-dependent. Given that current evidence is predominantly correlative and based on post-mortem and experimental studies, further longitudinal and mechanistic investigations are necessary.