CD4 + T细胞衰竭由高PD-1和LAG-3表达以及慢性乙型肝炎中辅助T细

StephenW

BMC Immunol. 2019 Aug 7;20(1):27. doi: 10.1186/s12865-019-0309-9.
CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B.
Dong Y1, Li X1, Zhang L1, Zhu Q1, Chen C2, Bao J1, Chen Y3,4.
Author information

1
    Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.
2
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.
3
    Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China. [email protected].
4
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China. [email protected].

Abstract
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.
KEYWORDS:

CD4+ T cells; Chronic HBV infection; Cytokine; Inhibitory molecules; Lymphocyte activation gene-3 (LAG-3); Programmed death 1 (PD-1)

PMID:
    31390978
DOI:
    10.1186/s12865-019-0309-9

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StephenW

BMC Immunol。 2019年8月7日; 20（1）：27。 doi：10.1186 / s12865-019-0309-9。
CD4 + T细胞衰竭由高PD-1和LAG-3表达以及慢性乙型肝炎中辅助T细胞功能的丧失所揭示。
董Y1，李X1，张L1，朱Q1，陈C2，包J1，陈Y 3,4。
作者信息

1
    浙江大学医学院第一附属医院浙江省临床体外诊断技术重点实验室，杭州市庆春路79号，310003
2
    浙江大学医学院附属第一医院感染性疾病诊疗协同创新中心，传染病诊疗国家重点实验室，杭州市庆春路79号，310003
3
    浙江大学医学院第一附属医院浙江省临床体外诊断技术重点实验室，杭州市庆春路79号，310003 [email protected]。
4
    浙江大学医学院附属第一医院感染性疾病诊疗协同创新中心，传染病诊疗国家重点实验室，杭州市庆春路79号，310003 [email protected]。

抽象
背景：

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，我们分析了程序性死亡-1（PD-1）和淋巴细胞活化基因-3（LAG-3）在CD4 + T细胞上的表达与HBV疾病进展之间的关系。
结果：

来自HBV患者的CD4 + T细胞的PD-1和LAG-3表达显着高于来自HC的患者。此外，在PD-1和LAG-3表达水平与ALT（丙氨酸氨基转移酶）水平之间发现显着的正相关。高PD-1和LAG-3水平抑制CD4 + T细胞功能，具有高PD-1和LAG-3表达的CD4 + T细胞丧失分泌IFN-γ，IL-2和TNF-α的能力。此外，阻断PD-1和LAG-3途径逆转了对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细胞衰竭具有高PD-1和LAG-3表达以及缺乏辅助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细胞功能部分恢复。
关键词：

CD4 + T细胞;慢性HBV感染;细胞因子;抑制分子;淋巴细胞活化基因-3（LAG-3）;程序性死亡1（PD-1）

结论：
    31390978
DOI：
    10.1186 / s12865-019-0309-9

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StephenW

https://bmcimmunol.biomedcentral ... 6/s12865-019-0309-9