干细胞衍生的病毒抗原特异性T细胞通过产生IFN-γ和TNF-⍺抑

StephenW

Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺
Mohammad Haque  1 , Fengyang Lei  2 , Xiaofang Xiong  1 , Yijie Ren  1 , Anil Kumar  1 , Jugal Kishore Das  1 , Xingcong Ren  3 , Deyu Fang  4 , Paul de Figueiredo  1 , Jin-Ming Yang  3 , Jianxun Song  5
Affiliations
Affiliations

    1
    Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA.
    2
    Department of Ophthalmology, Harvard Medical School, Boston, MA 02215, USA.
    3
    Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
    4
    Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
    5
    Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA. Electronic address: [email protected].

    PMID: 32679546 DOI: 10.1016/j.isci.2020.101333

Abstract

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress hepatitis B virus (HBV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the liver to suppress HBV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs provoke the antiviral response remain to be fully elucidated. In this study, we generated the functional HBV surface Ag-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the underlying mechanisms of the CTL-mediated antiviral replication in a murine model. We show that adoptive transfer of HBV surface Ag-specific iPSC-CTLs greatly suppressed HBV replication and prevented HBV surface Ag expression. We further demonstrate that the adoptive transfer significantly increased T cell accumulation and production of antiviral cytokines. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the liver and suppress HBV replication through producing antiviral cytokines.

Keywords: Functional Aspects of Cell Biology; Immunology.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement

Declaration of Interests The authors have declared that no conflict of interest exists.

StephenW

干细胞衍生的病毒抗原特异性T细胞通过产生IFN-γ和TNF-⍺抑制HBV复制
穆罕默德·哈克1，冯凤雷2，熊小芳1，任一杰1，阿尼尔·库马尔1，贾格尔·基肖尔·达斯1，邢杏任3，德裕芳4，保罗·德·菲格雷多1，杨金明3，建勋歌5
隶属关系
隶属关系

    1个
    得克萨斯州A＆M大学健康科学中心微生物发病机理和免疫学系，MREB II，美国德克萨斯州布莱恩市8447 Riverside Pkwy 3344室，美国德克萨斯州77807。
    2
    哈佛医学院眼科，美国马萨诸塞州02215。
    3
    肯塔基大学医学院毒理学和癌症生物学系，美国肯塔基州列克星敦40536。
    4
    西北大学芬伯格医学院病理学系，美国伊利诺斯州60611。
    5
    得克萨斯州A＆M大学健康科学中心微生物发病机理和免疫学系，MREB II，美国德克萨斯州布莱恩市8447 Riverside Pkwy 3344室，美国德克萨斯州77807。电子地址：[email protected]。

    PMID：32679546 DOI：10.1016 / j.isci.2020.101333

抽象

源自多能干细胞（PSC）的病毒抗原（Ag）特异性CD8 +细胞毒性T淋巴细胞（CTL），即PSC-CTL，具有抑制乙型肝炎病毒（HBV）感染的能力。过继转移后，PSC-CTL可以渗入肝脏以抑制HBV复制。尽管如此，病毒Ag特异性PSC-CTL激发抗病毒应答的机制仍有待充分阐明。在这项研究中，我们从诱导的PSC（iPSC）（即iPSC-CTL）生成了功能性HBV表面Ag特异性CTL，并研究了在小鼠模型中CTL介导的抗病毒复制的潜在机制。我们显示，HBV表面Ag特异性iPSC-CTL的过继转移极大地抑制了HBV复制并阻止了HBV表面Ag的表达。我们进一步证明了过继转移显着增加了T细胞的积累和抗病毒细胞因子的产生。这些结果表明，源自干细胞的病毒Ag特异的CTL可以在肝脏中稳固积累，并通过产生抗病毒细胞因子来抑制HBV复制。

关键词：细胞生物学的功能方面；免疫学。

版权所有©2020作者。由Elsevier Inc.出版。保留所有权利。
利益冲突声明

利益声明作者已经声明不存在利益冲突。

StephenW

https://www.cell.com/iscience/pd ... 04%3Fshowall%3Dtrue