Increasing LAG-3 expression suppresses T-cell function in chronic hepatitis B: A balance between immunity strength and liver injury extent.
Increasing LAG-3 expression suppresses T-cell function in chronic hepatitis B: A balance between immunity strength and liver injury extent.
复制标题
LAG-3表达增加抑制慢性乙型肝炎中T细胞功能免疫强度与肝损伤程度之间的平衡
DOI：
10.1097/md.0000000000005275
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发表时间：
2017-01
期刊：
影响因子：
1.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Ye B;Li X;Dong Y;Wang Y;Tian L;Lin S;Liu X;Kong H;Chen Y
弱的或缺乏病毒特异性CD8+T细胞对乙肝病毒感染的反应被认为是持续的乙肝病毒感染的原因。以往的研究表明，包括淋巴细胞激活基因-3(LAG-3)在内的多种抑制性受体可以抑制慢性病毒感染时CD8+T细胞的应答。本研究旨在检测慢性乙肝患者肝组织中LAG-3的表达，并探讨慢性乙肝患者免疫反应的调节方式，以平衡免疫反应的强度和肝损伤的程度。结果表明，慢性乙型病毒性肝炎患者免疫活动期CD8+T细胞中LAG-3的表达水平明显高于慢性无症状乙肝病毒携带者和健康对照组。在LAG-3高表达的细胞中，CD8+T细胞功能受到抑制，这些细胞表现出干扰素-γ(干扰素-γ)的分泌减少。此外，经抗LAG-3的特异性抗体处理后，CD8+T细胞的干扰素-γ的分泌恢复。综上所述，肝脏损伤在免疫活动期是突出的，但抑制T细胞功能可以减轻这种损伤。重要的是，使用LAG-3特异性抗体可以阻断LAG-3的抑制功能，这可以恢复不起作用的T细胞的活性。
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.