@article{4b5788c911a44cd79436afff8cc7f978,
title = "Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺",
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",
author = "Mohammad Haque and Fengyang Lei and Xiaofang Xiong and Yijie Ren and Anil Kumar and Das, {Jugal Kishore} and Xingcong Ren and Deyu Fang and {de Figueiredo}, Paul and Yang, {Jin Ming} and Jianxun Song",
note = "Funding Information: The authors thank Dr. Pei-Jer Chen from National Taiwan University Hospital for providing the pAAV/HBV1.2 construct and Dr. Adam J Gehring from Toronto General Hospital Research Institute for providing the s183-specific TCR genes. The authors also would like to acknowledge the critical review of the manuscript by Dr. Jianming Hu from The Pennsylvania State University College of Medicine. Guarantor's statement: J.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Funding/financial support: This work was supported by the National Institutes of Health Grant R01AI121180 and R21AI128325 to J.S. and R01CA221867 to J.-M.Y. and J.S. J.S. and J.-M.Y. designed the experiments, analyzed data, and contributed to the writing of the paper. M.H. F.L. Y.R. A.K. and J.K.D. performed the experiments. D.F. and P.d.F. provided reagents for the experiments. X.X. and X.R. analyzed data. The authors have declared that no conflict of interest exists. Funding Information: Funding/financial support: This work was supported by the National Institutes of Health Grant R01AI121180 and R21AI128325 to J.S. and R01CA221867 to J.-M.Y. and J.S. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = jul,
day = "24",
doi = "10.1016/j.isci.2020.101333",
language = "English (US)",
volume = "23",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "7",
}
