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.