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
Affiliations
Mohammad Haque
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA
Fengyang Lei
Department of Ophthalmology, Harvard Medical School, Boston, MA 02215, USA
Xiaofang Xiong
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA
Yijie Ren
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA
Anil Kumar
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA
Jugal Kishore Das
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA
Xingcong Ren
Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
Deyu Fang
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Paul de Figueiredo
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA
Jin-Ming Yang
Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
Jianxun Song
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, MREB II, Room 3344, 8447 Riverside Pkwy, Bryan, TX 77807, USA; Corresponding author
Summary: 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.
