Mucosal-associated invariant T-cells are severely reduced and exhausted in humans with chronic HBV infection
Mucosal-associated invariant T-cells are severely reduced and exhausted in humans with chronic HBV infection
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慢性 HBV 感染者中粘膜相关的不变 T 细胞严重减少并耗尽
DOI：
10.1111/jvh.13341
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发表时间：
2020-06-22
影响因子：
2.5
通讯作者：
Gao, Yifang
中科院分区：
文献类型：
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作者：
Huang, Wenyong;He, Wenjing;Gao, Yifang
慢性乙型肝炎病毒(CHBV)感染是导致肝脏疾病的主要原因。粘膜相关不变T细胞(MAIT)对于肝脏的抗病毒免疫是重要的，但CHBV感染患者鼻窦内和外周MAIT细胞之间的区别尚不清楚。PBMC来自CHBV感染者(n=29)和年龄匹配的对照组(n=46)。从健康供者(n=29)和患者的移植肝(n=19)采集肝相关单个核细胞(LMC)，用于表型、功能和TCR多样性分析。与对照组相比，CHBV感染组外周血和鼻窦内MAIT细胞的百分比均显著降低。CHBV感染者外周血MAIT细胞表达高水平的HLA-DR、CD69、CD38和PD-1。我们还证实了乙肝患者外周血MAIT细胞中T细胞耗竭基因的表达升高。除PD-1水平有差异外，两组肝MAIT细胞间无差异。CHBV感染者外周血MAIT细胞产生的干扰素-α明显低于对照组，而肝MAIT细胞则无明显差异。此外，在CHBV患者中发现了明显的TCR特征。因此，我们在CHBV感染患者的肝脏和外周MAIT细胞中发现了明显的活动和功能。
Chronic hepatitis B virus (CHBV) infection is a major cause of liver diseases. Mucosal-associated invariant T (MAIT) cells are important for antiviral immunity in the liver, but the distinction between intrasinusoidal and peripheral MAIT cells in patients with CHBV infections remains unclear. PBMCs were obtained from patients with CHBV infections (n = 29) and age-matched controls (n = 46). Liver-associated mononuclear cells (LMCs) were collected from healthy donors (n = 29) and explanted livers (n = 19) from patients and used for phenotypic, functional and TCR diversity analyses. The percentages of both peripheral and intrasinusoidal MAIT cells were significantly reduced in the CHBV infection group compared to the control group. Peripheral MAIT cells from CHBV-infected patients expressed higher levels of HLA-DR, CD69, CD38 and PD-1 than those of controls. We also confirmed that peripheral MAIT cells in HBV patients had elevated expression T-cell exhaustion genes. Except for a difference in the level of PD-1, no differences were observed between the liver MAIT cells of the two groups. The production of IFN-alpha in peripheral MAIT cells of CHBV infection patients was lower than in control patients, but no such difference was observed in liver MAIT cells. Additionally, a distinct TCR signature was found in CHBV patients. Hence, we found distinct activities and functions in liver and peripheral MAIT cells of patients with CHBV infections.