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TIM-3 作为慢性乙型肝炎活动期患者 CD8 T 细胞耗竭的标志物。

TIM-3 as a marker of exhaustion in CD8 T cells of active chronic hepatitis B patients.

机构信息

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

Infectious Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran.

出版信息

Microb Pathog. 2019 Mar;128:323-328. doi: 10.1016/j.micpath.2019.01.026. Epub 2019 Jan 17.

Abstract

BACKGROUND

Chronic HBV infection presents weak or no virus-specific T-cell responses, implying to an exhausted phenotype, characterized by overexpression of several inhibitory receptors. In the present study, it was aimed to characterize the panel of inhibitory molecules on the CD8 T cells in patients with active chronic HBV infection.

METHODS

In this study, 31 active and 32 inactive individuals with chronic HBV infection were recruited. Peripheral blood mononuclear cells were isolated and a multicolor flow cytometry was applied to evaluate the surface inhibitory molecules of TIM3, PD-1, and CD39.

RESULTS

CD8 T cells expressing TIM3 were significantly higher in cases with active chronic HBV infection compared to inactive chronic HBV group (8.43 ± 1.4 vs. 5.15 ± 1.43; P < 0.0001). CD8TIM3PD-1 T cells were significantly higher in active chronic HBV cases in comparison to the inactive chronic HBV subjects (4.26 ± 1.04 vs. 3.41 ± 0.74; P < 0.001). Different subpopulations of the CD8 T cells were correlated with the duration of infection and HBV DNA load in the cases with active chronic HBV infection.

CONCLUSION

It appears that CD8 TIM3 T cells are the major exhausted phenotype of T cells during the active state of HBV infection.

摘要

背景

慢性乙型肝炎病毒(HBV)感染表现出较弱或无病毒特异性 T 细胞反应,暗示存在衰竭表型,其特征是表达多种抑制性受体。本研究旨在描述慢性 HBV 感染患者中 CD8 T 细胞上抑制性分子的特征。

方法

本研究招募了 31 名慢性 HBV 感染的活动期和 32 名非活动期患者。分离外周血单核细胞,并应用多色流式细胞术评估 TIM3、PD-1 和 CD39 的表面抑制性分子。

结果

与非活动性慢性 HBV 组相比,活动性慢性 HBV 感染患者的 CD8 T 细胞表达 TIM3 显著升高(8.43±1.4 比 5.15±1.43;P<0.0001)。与非活动性慢性 HBV 患者相比,活动性慢性 HBV 患者的 CD8 TIM3 PD-1 T 细胞显著升高(4.26±1.04 比 3.41±0.74;P<0.001)。在活动期慢性 HBV 感染患者中,不同亚群的 CD8 T 细胞与感染持续时间和 HBV DNA 载量相关。

结论

在 HBV 感染的活动期,CD8 TIM3 T 细胞似乎是 T 细胞衰竭表型的主要表现。

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