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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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/1999-4915/13/5/753 |
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| author | Mohammad Haque Fengyang Lei Xiaofang Xiong Yijie Ren Hao-Yun Peng Liqing Wang Anil Kumar Jugal Kishore Das Jianxun Song |
| author_facet | Mohammad Haque Fengyang Lei Xiaofang Xiong Yijie Ren Hao-Yun Peng Liqing Wang Anil Kumar Jugal Kishore Das Jianxun Song |
| author_sort | Mohammad Haque |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T11:58:33Z |
| format | Article |
| id | doaj.art-07472626e79b4b819cd1ca1a4e90cfef |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T11:58:33Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-07472626e79b4b819cd1ca1a4e90cfef2023-11-21T17:05:15ZengMDPI AGViruses1999-49152021-04-0113575310.3390/v13050753Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T CellsMohammad Haque0Fengyang Lei1Xiaofang Xiong2Yijie Ren3Hao-Yun Peng4Liqing Wang5Anil Kumar6Jugal Kishore Das7Jianxun Song8Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Ophthalmology, Harvard University School of Medicine, Boston, MA 02215, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USAThe 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.https://www.mdpi.com/1999-4915/13/5/753HIVstem cellscell differentiationT cellsviral antigenviral replication |
| spellingShingle | Mohammad Haque Fengyang Lei Xiaofang Xiong Yijie Ren Hao-Yun Peng Liqing Wang Anil Kumar Jugal Kishore Das Jianxun Song Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells Viruses HIV stem cells cell differentiation T cells viral antigen viral replication |
| 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 | HIV stem cells cell differentiation T cells viral antigen viral replication |
| url | https://www.mdpi.com/1999-4915/13/5/753 |
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