Stem cell-derived viral antigen-specific t cells suppress hiv replication and pd-1 expression on cd4+ t cells

Mohammad Haque, Fengyang Lei, Xiaofang Xiong, Yijie Ren, Hao Yun Peng, Liqing Wang, Anil Kumar, Jugal Kishore Das, Jianxun Song

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripo-tent 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.

Original languageEnglish (US)
Article number753
JournalViruses
Volume13
Issue number5
DOIs
StatePublished - May 2021

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

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