Cd8(+) T Cells Specific To Apoptosis-Associated Epitopes Are Expanded In Patients With Chronic Hbv Infection And Fibrosis

Background & Aims During chronic viral infections, the apoptosis of activated T cell elicits a CD8(+) T cell response directed to those cryptic epitopes that emerge from caspase-cleaved structural proteins. Such response directed to apoptosis-associated epitopes (AEs) contributes to the amplification of immunopathology.Methods Here, we have analysed through flow cytometry AE-specific CD8(+) T cells in patients with chronic hepatitis B virus (HBV) infection, naive-to-treatment or undergoing nucleos(t)ide-analogue (NUC) therapy.Results We found that AE-specific CD8(+) T cell frequencies were significantly increased only in those NUC-treated patients who also presented advanced hepatic fibrosis. Regulatory T cells were also expanded in those patients, and AE-specific, but not HBV-specific, CD8(+) T cell frequency positively correlated with Treg percentages. Through multiparameter flow cytometry, multidimensionality reduction and unsupervised clustering analysis, we could identify novel subpopulations among effector memory (em) and emCD45RA(+) T cell (Tem and Temra) subsets. CD8(+) T cells with distinct specificities differentially populated the subpopulation map: while HBV-specific were mostly contained in the Tem subset, AE-specific CD8(+) T cells encompassed naive, as well as T central memory, Tem and Temra cells.Conclusion All together, these findings indicate a link between AE-specific CD8(+) T cells and advanced liver fibrosis in patients with chronic HBV infection, and suggest that virus-specific and AE-specific CD8(+) T cells exhibit distinct differentiation states and contribute in distinct ways to immunopathology.