Interleukin-33-induced immune tolerance is associated with the imbalance of memory and naïve T-lymphocyte subsets

Abstract

The current study aimed to investigate the distribution of memory and naïve T cell (TN) subsets in hepatitis B virus (HBV)-infected patients at different immune stages and investigate the effect of interleukin 33 (IL-33) on the regulation of the T-cell subsets. The distributions of memory and naïve T cells were detected by flow cytometry. ELISA was conducted to assess the levels of IL-4, IL-5, IL-10, IL-12, interferon and tumor necrosis factor. The expression levels of IL-33 and HBV x protein (HBx) were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. By detecting TNs, central memory T cells (TCM) and effector memory T cells (TEM), it was identified that the proportions of TCM and TEM in CD4+ T cells were increased in patients with HBV. The trend observed for levels of CD8+ TCM and TEM was similar to that of CD4+ T cells in the immune tolerance and immune activation groups, however CD8+ TCM and TEM were significantly reduced in patients who underwent treatment. The CD8+ TEM cells appeared to be more sensitive to HBV activation and drug therapy. In addition, IL-33 stimulation was observed to induce imbalances of CD8+ TN and CD8+ TEM, and while the imbalances were directly regulated by HBx, IL-33 was not a key factor for the expression of HBx. CD8+ TEM cells may be a sensitive marker to assess the immune state of patients with HBV and the effect of clinical therapy. Treatment targeting IL-33 may be a potential method to reverse HBV-induced immune tolerance.