Table 1. NK cell characteristics in... | Rockefeller University Press

Table 1.

NK cell characteristics in neurodegenerative diseases

Disease	Circulating NK cells	CSF NK cells	CNS parenchyma NK cells	Predominant phenotype	Activation/functional status	Protective mechanisms	Detrimental effects
MS	Altered number	↑	↑ Accumulate in active lesions near T cells	CD56^bright	Variable cytolytic activity during relapses	Kills autoreactive CD4⁺ T cells; secretes acetylcholine and immunosuppressive cytokines; NKG2C⁺ and NKG2D⁺ subsets eliminate EBV-induced autoreactive clones	NKp46⁺/NK1.1⁺ ILCs promote brain barrier permeabilization and T cell CNS entry; autoreactive B cells evade killing via HLA-E upregulation
AD	Unchanged	↑	Not well defined	CD56^bright (predominant in CNS)	Proinflammatory in CSF during MCI; variable blood; NK cytotoxicity (increased to impaired)	Direct uptake/degradation of Aβ; restores microglial phagocytosis; reduces neuroinflammation; meningeal NK-derived IFN-γ promotes memory formation	Chronic activation leads to overproduction of IFN-γ and TNF-α (inversely correlates with cognition); depletion in mouse models reduces neuroinflammation but impairs early protective effects
PD	↑	↑	↑ Infiltrate substantia nigra; colocalize with α-syn aggregates and dopaminergic neurons	CD56^dim (blood)	Elevated activation markers; correlates with severity/progression	Clear α-syn aggregates; likely eliminates autoreactive T cells	α-syn clearance reduces NK cytolytic capacity and IFN-γ secretion, potential dysfunction with chronic activation

Disease	Circulating NK cells	CSF NK cells	CNS parenchyma NK cells	Predominant phenotype	Activation/functional status	Protective mechanisms	Detrimental effects
MS	Altered number	↑	↑ Accumulate in active lesions near T cells	CD56^bright	Variable cytolytic activity during relapses	Kills autoreactive CD4⁺ T cells; secretes acetylcholine and immunosuppressive cytokines; NKG2C⁺ and NKG2D⁺ subsets eliminate EBV-induced autoreactive clones	NKp46⁺/NK1.1⁺ ILCs promote brain barrier permeabilization and T cell CNS entry; autoreactive B cells evade killing via HLA-E upregulation
AD	Unchanged	↑	Not well defined	CD56^bright (predominant in CNS)	Proinflammatory in CSF during MCI; variable blood; NK cytotoxicity (increased to impaired)	Direct uptake/degradation of Aβ; restores microglial phagocytosis; reduces neuroinflammation; meningeal NK-derived IFN-γ promotes memory formation	Chronic activation leads to overproduction of IFN-γ and TNF-α (inversely correlates with cognition); depletion in mouse models reduces neuroinflammation but impairs early protective effects
PD	↑	↑	↑ Infiltrate substantia nigra; colocalize with α-syn aggregates and dopaminergic neurons	CD56^dim (blood)	Elevated activation markers; correlates with severity/progression	Clear α-syn aggregates; likely eliminates autoreactive T cells	α-syn clearance reduces NK cytolytic capacity and IFN-γ secretion, potential dysfunction with chronic activation