Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺

Mohammad Haque, Fengyang Lei, Xiaofang Xiong, Yijie Ren, Anil Kumar, Jugal Kishore Das, Xingcong Ren, Deyu Fang, Paul de Figueiredo, Jin Ming Yang, Jianxun Song*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number101333
JournaliScience
Volume23
Issue number7
DOIs
StatePublished - Jul 24 2020

Keywords

  • Functional Aspects of Cell Biology
  • Immunology

ASJC Scopus subject areas

  • General

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    Haque, M., Lei, F., Xiong, X., Ren, Y., Kumar, A., Das, J. K., Ren, X., Fang, D., de Figueiredo, P., Yang, J. M., & Song, J. (2020). Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺. iScience, 23(7), [101333]. https://doi.org/10.1016/j.isci.2020.101333