BACKGROUND Immune inhibitory receptors play an important role in chronic infections. However, little is known about their role in hepatitis B virus (HBV) infection. Here, we analyzed the relationship between programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) expression on CD4+ T cells and HBV disease progression. RESULTS PD-1 and LAG-3 expression was significantly higher on CD4+ T cells from HBV patients than on those from the HCs. In addition, a significant positive correlation was found between the PD-1 and LAG-3 expression levels and the ALT(alanine aminotransferase) level. CD4+ T cell function was inhibited by high PD-1 and LAG-3 levels, and CD4+ T cells with high PD-1 and LAG-3 expression lost the ability to secrete IFN-γ, IL-2 and TNF-α. Furthermore, blockade of the PD-1 and LAG-3 pathways reversed the damage to CD4+ T cell proliferation and cytokine secretion. CONCLUSIONS CD4+ T cell exhaustion during chronic HBV had high PD-1 and LAG-3 expression and the absence of helper T cell cytokines, including IFN-γ, IL-2 and TNF-α. After blocking PD-L1 and LAG-3, CD4+ T cell function in chronic hepatitis B patients was partially restored.

中文翻译：

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慢性乙型肝炎的高PD-1和LAG-3表达以及辅助性T细胞功能的丧失揭示了CD4 + T细胞的衰竭。

背景技术免疫抑制受体在慢性感染中起重要作用。然而，关于它们在乙型肝炎病毒（HBV）感染中的作用知之甚少。在这里，我们分析了CD4 + T细胞上程序性死亡1（PD-1）和淋巴细胞活化基因3（LAG-3）表达与HBV疾病进展之间的关系。结果HBV患者CD4 + T细胞的PD-1和LAG-3表达明显高于HCs患者。另外，在PD-1和LAG-3表达水平与ALT（丙氨酸转氨酶）水平之间发现显着正相关。高PD-1和LAG-3抑制CD4 + T细胞功能，高PD-1和LAG-3表达的CD4 + T细胞失去分泌IFN-γ，IL-2和TNF-α的能力。此外，PD-1和LAG-3途径的阻断可逆转CD4 + T细胞增殖和细胞因子分泌的损害。结论慢性HBV期间CD4 + T细胞衰竭的PD-1和LAG-3表达高，并且缺乏辅助性T细胞细胞因子，包括IFN-γ，IL-2和TNF-α。阻断PD-L1和LAG-3后，慢性乙型肝炎患者的CD4 + T细胞功能得以部分恢复。