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

IScience
Mohammad HaqueJianxun Song

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.

References

Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F V ChisariR L Brinster
Nov 5, 2002·Annual Review of Immunology·Phillip Wong, Eric G Pamer
Jun 9, 2004·The Journal of Experimental Medicine·Qizhi TangJeffrey A Bluestone
Apr 6, 2005·The Journal of Experimental Medicine·Iris LeeWayne W Hancock
Nov 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·John M MurrayFrancis V Chisari
Nov 11, 2006·Proceedings of the National Academy of Sciences of the United States of America·Li-Rung HuangDing-Shinn Chen
Feb 11, 2009·Cell·Jeong Beom KimHans R Schöler
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christian S HinrichsNicholas P Restifo
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marleen M van LoenenMirjam H M Heemskerk
Apr 19, 2011·Journal of Immunotherapy·Sid P KerkarNicholas P Restifo
Jun 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rizwanul HaqueJianxun Song
Jul 16, 2013·PLoS Pathogens·Masanori IsogawaFrancis V Chisari
Dec 18, 2013·Science Translational Medicine·Victor D FedorovMichel Sadelain
Apr 30, 2014·Cancer Immunology Research·Marcela V MausCarl H June
Sep 17, 2014·The Journal of Experimental Medicine·Peter D KurktschievNorbert H Gruener
Dec 15, 2015·The Journal of Clinical Investigation·Christopher A KlebanoffNicholas P Restifo
Jan 19, 2016·Cell Transplantation·Mohammad HaqueJianxun Song
Jul 18, 2016·Journal of Hepatology·Alexandre Pierre Benechet, Matteo Iannacone
Apr 30, 2017·Frontiers in Immunology·Praneet SandhuJianxun Song
Dec 7, 2018·Journal of Virology·Atefeh KhakpoorAntonio Bertoletti
May 1, 2019·The Journal of Clinical Investigation·Karin WisskirchenUlrike Protzer
Oct 5, 2019·Nature·Alexandre P BénéchetMatteo Iannacone

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
PCR
flow cytometry
ELISA
transgenic

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.