IL‐15‐induced CD38+HLA‐DR+CD8+ T cells correlate with liver injury via NKG2D in chronic hepatitis B cirrhosis

Abstract Objectives CD8+ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38+HLA‐DR+CD8+ T cells, or bystander‐activated CD8+ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38+HLA‐DR+CD8+ T cell‐mediated pathogenesis during liver cirrhosis. Methods The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity‐related indicators of CD38+HLA‐DR+CD8+ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38+HLA‐DR+CD8+ T‐cell killing was detected using cytotoxicity and antibody‐blocking assays. Results The proportion of CD38+HLA‐DR+CD8+ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate‐like functional characteristics. This CD8+ T‐cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity‐related cytokines, granzyme B and perforin. IL‐15 promoted CD38+HLA‐DR+CD8+ T‐cell activation and proliferation, inducing significant TCR‐independent cytotoxicity mediated through NKG2D. Conclusions CD38+HLA‐DR+CD8+ T cells correlated with cirrhosis‐related liver injury and contributed to liver damage by signalling through NKG2D in a TCR‐independent manner.