TY - JOUR
T1 - Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺
AU - Haque, Mohammad
AU - Lei, Fengyang
AU - Xiong, Xiaofang
AU - Ren, Yijie
AU - Kumar, Anil
AU - Das, Jugal Kishore
AU - Ren, Xingcong
AU - Fang, Deyu
AU - de Figueiredo, Paul
AU - Yang, Jin Ming
AU - Song, Jianxun
N1 - Publisher Copyright:
© 2020 The Author(s)
PY - 2020/7/24
Y1 - 2020/7/24
N2 - 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.
AB - 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.
KW - Functional Aspects of Cell Biology
KW - Immunology
UR - http://www.scopus.com/inward/record.url?scp=85087827899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087827899&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101333
DO - 10.1016/j.isci.2020.101333
M3 - Article
AN - SCOPUS:85087827899
SN - 2589-0042
VL - 23
JO - iScience
JF - iScience
IS - 7
M1 - 101333
ER -
