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Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells

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 the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV repli...

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Autores principales: Haque, Mohammad, Lei, Fengyang, Xiong, Xiaofang, Ren, Yijie, Peng, Hao-Yun, Wang, Liqing, Kumar, Anil, Das, Jugal Kishore, Song, Jianxun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146941/
https://www.ncbi.nlm.nih.gov/pubmed/33923025
http://dx.doi.org/10.3390/v13050753
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author Haque, Mohammad
Lei, Fengyang
Xiong, Xiaofang
Ren, Yijie
Peng, Hao-Yun
Wang, Liqing
Kumar, Anil
Das, Jugal Kishore
Song, Jianxun
author_facet Haque, Mohammad
Lei, Fengyang
Xiong, Xiaofang
Ren, Yijie
Peng, Hao-Yun
Wang, Liqing
Kumar, Anil
Das, Jugal Kishore
Song, Jianxun
author_sort Haque, Mohammad
collection PubMed
description 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 the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs elicit the antiviral response remain to be fully elucidated. In this study, we generated the functional HIV-1 Gag epitope SL9-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the suppression of SL9-specific iPSC-CTLs on viral replication and the protection of CD4+ T cells. A chimeric HIV-1, i.e., EcoHIV, was used to produce HIV replication in mice. We show that adoptive transfer of SL9-specific iPSC-CTLs greatly suppressed EcoHIV replication in the peritoneal macrophages and spleen in the animal model. Furthermore, we demonstrate that the adoptive transfer significantly reduced expression of PD-1 on CD4+ T cells in the spleen and generated persistent anti-HIV memory T cells. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the local tissues to suppress HIV replication and prevent CD4+ T cell exhaustion through reduction of PD-1 expression.
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spelling pubmed-81469412021-05-26 Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells Haque, Mohammad Lei, Fengyang Xiong, Xiaofang Ren, Yijie Peng, Hao-Yun Wang, Liqing Kumar, Anil Das, Jugal Kishore Song, Jianxun Viruses Article 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 the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs elicit the antiviral response remain to be fully elucidated. In this study, we generated the functional HIV-1 Gag epitope SL9-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the suppression of SL9-specific iPSC-CTLs on viral replication and the protection of CD4+ T cells. A chimeric HIV-1, i.e., EcoHIV, was used to produce HIV replication in mice. We show that adoptive transfer of SL9-specific iPSC-CTLs greatly suppressed EcoHIV replication in the peritoneal macrophages and spleen in the animal model. Furthermore, we demonstrate that the adoptive transfer significantly reduced expression of PD-1 on CD4+ T cells in the spleen and generated persistent anti-HIV memory T cells. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the local tissues to suppress HIV replication and prevent CD4+ T cell exhaustion through reduction of PD-1 expression. MDPI 2021-04-25 /pmc/articles/PMC8146941/ /pubmed/33923025 http://dx.doi.org/10.3390/v13050753 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Haque, Mohammad
Lei, Fengyang
Xiong, Xiaofang
Ren, Yijie
Peng, Hao-Yun
Wang, Liqing
Kumar, Anil
Das, Jugal Kishore
Song, Jianxun
Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells
title Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells
title_full Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells
title_fullStr Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells
title_full_unstemmed Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells
title_short Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells
title_sort stem cell-derived viral antigen-specific t cells suppress hiv replication and pd-1 expression on cd4+ t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146941/
https://www.ncbi.nlm.nih.gov/pubmed/33923025
http://dx.doi.org/10.3390/v13050753
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