Increased Granzyme K⁺ CD8⁺ T cells and senescent subset in Behçet's disease

Behçet's disease (BD) is a chronic inflammatory condition with immune system dysregulation. Recent evidence suggests proinflammatory roles of extracellular granzyme K (GzmK), particularly in aged immune cells. This study investigated GzmK-expressing CD8⁺ T cells and their senescent subset in BD pathology.

We analysed lymphocyte subsets in blood samples from 19 active BD (aBD), 19 inactive BD (iaBD), and 19 healthy controls (HC) using flow cytometry and granzymes, as well as IL-6 using enzyme-linked immunosorbent assay.

Active BD patients showed significantly higher serum GzmK levels and GzmK⁺CD8⁺ T cells with advanced differentiation markers. GzmK⁺CD8⁺ T cells positively correlated with TNF-α⁺ and IFN-γ⁺ lymphocytes. The senescent subset (GzmK⁺CD27^-CD28^-CD57⁺CD8⁺) specifically correlated with TNF-α⁺ lymphocytes, indicating involvement in TNF-α-centered inflammatory pathways.

GzmK⁺CD8⁺ T cells and their senescent counterparts are not merely biomarkers of disease activity but may function as extracellular proinflammatory effectors that amplify the TNF-α-mediated inflammatory loop in BD. Targeting the GzmK-senescence axis represents a promising therapeutic strategy for managing chronic inflammation in BD.