Intestinal CD8+ γδ T cells shift from immune activation to suppression, with concomitant impairment of cytotoxicity as disease activity increases in patients with ulcerative colitis

Introduction Ulcerative colitis (UC) is a persistent inflammatory intestinal condition characterized by fluctuating disease activity (DA), with incompletely understood immunopathogenesis. Material and methods Our analysis included employing flow cytometry to examine CD8+ γδ T cells in the intestinal mucosa (IM) and the peripheral blood (PB) of UC patients as well as healthy controls. We focused on the presence of the HLA-DR activation indicator, the PD-1 immune suppression component, and the cytotoxic elements TRAIL, granzyme B, and perforin within CD8+ γδ T cells. Results A marked decline in the levels of IM CD8+ γδ T cells with increasing UC DA was observed. The immune status of these cells transitioned from activation in individuals with moderate UC activity to suppression in those experiencing severe UC activity. Correspondingly, cytotoxicity, indicated by granzyme B and perforin levels, was impaired in patients with severe UC activity. Notably, the proportions of IM CD8+ γδ T cells expressing granzyme B, PD-1, and HLA-DR were identified as potential biomarkers for distinguishing disease severity. Conclusions Our findings demonstrate the progression from immune activation to suppression and the concomitant impairment of cytotoxic activity in intestinal CD8+ γδ T cells as DA increases in UC, which may have implications for disease monitoring and therapeutic intervention.