干扰素α以B细胞依赖性方式促进抗HBV细胞免疫反应

StephenW

干扰素α以B细胞依赖性方式促进抗HBV细胞免疫反应
钟世宏 1 , 李琼 1 , 文春华 1 , 李逸凡 1 , 杨舟 1 , 金子涵 1 , 郭富业 1 , 赵燕达 2 , 金林侯 3 , 永银李 4 , 李博堂 5
隶属关系
隶属关系

    1
    器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室，南方医科大学南方医院传染病科，广州，中国。
    2
    南方医科大学基础医学学院，广州，中国。
    3
    器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室，南方医科大学南方医院传染病科，广州，中国。电子地址：[email protected]。
    4
    器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室，南方医科大学南方医院传染病科，广州，中国。电子地址：[email protected]。
    5
    器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室，南方医科大学南方医院传染病科，广州，中国。电子地址：[email protected]。

    PMID：36165866 DOI：10.1016/j.antiviral.2022.105420

抽象的

目的：剖析干扰素 α (IFN-α) 介导的 T 细胞重塑的潜在机制对于实现慢性乙型肝炎 (CHB) 患者的最佳治疗反应是必不可少的。然而，在这个过程中对 B 细胞知之甚少。本研究旨在阐明 B 细胞在 IFN-α 介导的抗乙型肝炎病毒 (HBV) 细胞免疫中的作用。

方法：在 B 细胞缺陷小鼠模型中研究 B 细胞对 IFN-α 介导的 T 细胞反应的影响，并通过 HBV 和 IFN-α 质粒流体动力学注射。进行单细胞 RNA 测序以剖析 B 细胞和 T 细胞亚群之间的串扰以及来自 IFN-α 治疗的 CHB 患者的纵向血液样本的潜在分子和途径特征。

结果：B 细胞耗竭损害了功能性 T 细胞亚群，包括 HBV 特异性 CD8+ T 细胞，并导致 HBV 清除延迟。 IFN-α 治疗增强了 HBV 特异性 CD8+ T 细胞的反应，而这种作用在 B 细胞缺陷小鼠中消失了。潜在机制与 IFN-α 增强的 B 细胞与 T 细胞的连接有关，这是由 B 细胞中的抗原呈递和共刺激功能介导的。

结论：IFN-α 以 B 细胞依赖性方式协调保护性 HBV 特异性细胞免疫。

关键词：B细胞；细胞免疫；乙型肝炎病毒;干扰素-α； T细胞。

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利益冲突声明

竞争利益声明 作者声明该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。

StephenW

Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner
Shihong Zhong  1 , Qiong Li  1 , Chunhua Wen  1 , Yifan Li  1 , Yang Zhou  1 , Zihan Jin  1 , Guofu Ye  1 , Yanda Zhao  2 , Jinlin Hou  3 , Yongyin Li  4 , Libo Tang  5
Affiliations
Affiliations

    1
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    2
    School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
    3
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
    4
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].
    5
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].

    PMID: 36165866 DOI: 10.1016/j.antiviral.2022.105420

Abstract

Objectives: Dissecting the underlying mechanism of T cells remodeling mediated by interferon α (IFN-α) is indispensable for achieving an optimum therapeutic response in chronic hepatitis B (CHB) patients. However, little is known about B cells in this process. This study aims to elucidate the roles of B cells in IFN-α-mediated anti-hepatitis B virus (HBV) cellular immunity.

Method: The effects of B cells on IFN-α-mediated T cell response were investigated in B cell-deficient mouse model with HBV and IFN-α plasmid hydrodynamic injection. Single-cell RNA sequencing was performed to dissect the crosstalk among B cell and T cell subsets and the underlying molecule and pathway signatures on longitudinal blood samples from IFN-α-treated CHB patients.

Results: B cell depletion impaired the functional T cell subsets, including HBV-specific CD8+ T cells, and engendered a delayed HBV clearance. IFN-α treatment boosted the response of HBV-specific CD8+ T cells, whereas such effects disappeared in B cell-deficient mice. The underlying mechanisms were associated with IFN-α-reinforced connections of B cells toward T cells as mediated by the antigen presentation and costimulatory functions in B cells.

Conclusion: IFN-α orchestrates protective HBV-specific cellular immunity in a B cell-dependent manner.

Keywords: B cell; Cellular immunity; Hepatitis B virus; IFN-α; T cell.

Copyright © 2022 Elsevier B.V. All rights reserved.
Conflict of interest statement

Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.