Ye Bo, Li Xuefen, Dong Yuejiao, Wang Yiyin, Tian Li, Lin Sha, Liu Xia, Kong Haishen, Chen Yu
Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Medicine (Baltimore). 2017 Jan;96(1):e5275. doi: 10.1097/MD.0000000000005275.
Weak or absent virus-specific CD8 T-cell responses to hepatitis B virus (HBV) infection are thought to be responsible for persistent HBV infection. Previous studies have indicated that multiple inhibitory receptors, including lymphocyte activation gene-3 (LAG-3), can suppress the CD8 T-cell response in chronic viral infection. This study aimed to detect LAG-3 expression and to investigate the manner in which the immune response is regulated to balance the strength of the response with the extent of liver injury in chronic HBV infection. The results showed that LAG-3 expression levels were significantly higher in CD8 T cells from chronic hepatitis B patients in the immune-active phase compared with chronic asymptomatic HBV carriers and healthy controls. CD8 T-cell function was suppressed in cells with high LAG-3 expression, and these cells exhibited reduced interferon-γ (IFN-γ) secretion. Furthermore, IFN-γ secretion was restored in CD8 T cells that were treated with a specific antibody to LAG-3. Taken together, liver injury was prominent in the immune-active phase, but suppressing T-cell function could mitigate this damage. Importantly, the inhibitory function of LAG-3 can be blocked using a LAG-3-specific antibody, and this can restore the activity of non-functional T cells.
对乙型肝炎病毒（HBV）感染的病毒特异性CD8 T细胞反应较弱或缺失被认为是导致HBV持续感染的原因。先前的研究表明，包括淋巴细胞活化基因3（LAG-3）在内的多种抑制性受体可在慢性病毒感染中抑制CD8 T细胞反应。本研究旨在检测LAG-3的表达，并研究在慢性HBV感染中免疫反应是如何被调节以平衡反应强度与肝损伤程度的。结果显示，与慢性无症状HBV携带者及健康对照相比，免疫活动期慢性乙型肝炎患者的CD8 T细胞中LAG-3表达水平显著更高。LAG-3高表达的细胞中CD8 T细胞功能受到抑制，且这些细胞的干扰素-γ（IFN-γ）分泌减少。此外，用LAG-3特异性抗体处理的CD8 T细胞中IFN-γ分泌得以恢复。综上所述，肝损伤在免疫活动期较为突出，但抑制T细胞功能可减轻这种损伤。重要的是，使用LAG-3特异性抗体可阻断LAG-3的抑制功能，且这可恢复无功能T细胞的活性。
