Hepatitis B virus induces T cell exhaustion by increasing mitochondrial ROS accumulation.

This study seeks to examine the fluctuating levels of mitochondrial reactive oxygen species (ROS) in peripheral blood T cells of individuals with chronic hepatitis B (CHB) and their immunological implications. The study encompassed 95 participants, consisting of 23 healthy volunteers and 72 HBV-infected individuals positive for HBsAg. The study conducted a prospective analysis of HBV-DNA levels in the peripheral blood of patients. Flow cytometry was utilized to evaluate mitochondrial ROS levels and programmed death receptor-1 (PD-1) expression in T cells. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify γ-interferon (IFN-γ) levels in the plasma of individuals infected with HBV.The study revealed a positive correlation between ROS levels generated by CD8 and CD4 T cells and serum HBV-DNA load (p < 0.05). In comparison to the healthy control group (HC), CHB patients exhibited a notable increase in the proportion of CD8 and CD4 T cells expressing the exhaustion marker PD-1 in peripheral blood (p < 0.05). Furthermore, ROS levels produced by T cell subpopulations expressing PD-1 were significantly elevated compared to those not expressing PD-1 (p < 0.05). Additionally, plasma levels of IFN-γ were significantly inversely associated with serum HBV-DNA load and ROS production by CD8 T cells (p < 0.05).These findings indicate that an elevated viral load in individuals with CHB is closely linked to the accumulation of mitochondrial ROS in T cells. We observed that this ROS accumulation is concurrent with increased PD-1 expression and reduced IFN-γ production. Therefore, we hypothesize that mitochondrial dysfunction may be a key factor driving T cell exhaustion in this setting.