Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783697514235428864 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8146941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT haquemohammad stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT leifengyang stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT xiongxiaofang stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT renyijie stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT penghaoyun stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT wangliqing stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT kumaranil stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT dasjugalkishore stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells AT songjianxun stemcellderivedviralantigenspecifictcellssuppresshivreplicationandpd1expressiononcd4tcells |