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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.