靶向线粒体功能障碍可以恢复慢性乙型肝炎患者HBV特异性CD8 T

StephenW

Nature Medicine | Article

   

Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B

    Paola Fisicaro,    Valeria Barili,    Barbara Montanini,    Greta Acerbi,    Manuela Ferracin,    Francesca Guerrieri,    Debora Salerno,    Carolina Boni,    Marco Massari,    M Cristina Cavallo,    Glenda Grossi,    Tiziana Giuberti,    Pietro Lampertico,    Gabriele Missale,    Massimo Levrero,    Simone Ottonello    & Carlo Ferrari   

    Affiliations
    Contributions
    Corresponding author

    Nature Medicine
    23,
    327–336
    (2017)
    doi:10.1038/nm.4275

Received
    01 March 2016
Accepted
    04 January 2017
Published online
    06 February 2017

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Abstract

    Abstract• Accession codes• References• Author information• Supplementary information

Hepatitis B virus (HBV)-specific CD8 T cells are functionally exhausted in chronic hepatitis B infection, and this condition can be corrected only partially through the modulation of inhibitory pathways, which suggests that a more complex molecular interplay underlies T cell exhaustion. To gain broader insight into this process and identify additional targets for the restoration of T cell function, we compared the transcriptome profiles of HBV-specific CD8 T cells from patients with acute and chronic disease with those of HBV-specific CD8 T cells from patients able to resolve HBV infection spontaneously and influenza (FLU)-specific CD8 T cells from healthy participants. The results indicate that exhausted HBV-specific CD8 T cells are markedly impaired at multiple levels and show substantial downregulation of various cellular processes centered on extensive mitochondrial alterations. A notable improvement of mitochondrial and antiviral CD8 functions was elicited by mitochondrion-targeted antioxidants, which suggests a central role for reactive oxygen species (ROS) in T cell exhaustion. Thus, mitochondria represent promising targets for novel reconstitution therapies to treat chronic hepatitis B infection.
Subject terms:

    Immunology
    Viral infection

StephenW

自然医学|文章

   

靶向线粒体功能障碍可以恢复慢性乙型肝炎患者HBV特异性CD8 T细胞的抗病毒活性

    Paola Fisicaro，Valeria Barili，Barbara Montanini，Greta Acerbi，Manuela Ferracin，Francesca Guerrieri，Debora Salerno，Carolina Boni，Marco Massari，M Cristina Cavallo，Glenda Grossi，Tiziana Giuberti，Pietro Lampertico，Gabriele Missale，Massimo Levrero，Simone Ottonello＆Carlo法拉利

    关联
    贡献
    通讯作者

    自然医学
    如图23所示，
    327-336
    （2017年）
    doi：10.1038 / nm.4275

收到
    2016年3月1日
公认
    2017年1月4日
在线发布
    2017年2月6日

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抽象

    摘要•加入码•参考文献•作者信息•补充信息

乙型肝炎病毒（HBV）特异性CD8 T细胞在慢性乙型肝炎感染中功能性耗尽，并且这种病症可以通过抑制性途径的调节仅部分校正，这表明更复杂的分子相互作用是T细胞衰竭的基础。为了获得更广泛的洞察这个过程和确定额外的目标恢复T细胞功能，我们比较HBV特异性CD8 T细胞从急性和慢性疾病患者的转录组配置文件从那些HBV特异性CD8 T细胞从患者能以自发解决HBV感染和来自健康参与者的流感（FLU）特异性CD8 T细胞。结果表明，耗尽的HBV特异性CD8 T细胞在多个水平上显着受损，并且显示出以广泛的线粒体改变为中心的各种细胞过程的显着下调。线粒体靶向抗氧化剂引起线粒体和抗病毒CD8功能的显着改善，这表明活性氧（ROS）在T细胞衰竭中的中心作用。因此，线粒体代表新的重建治疗慢性乙型肝炎感染的有希望的目标。
主题词：

    免疫学
    病毒感染