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  • Frontiers Media SA  (6)
  • Song, Jin-Wen  (6)
  • 2020-2024  (6)
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  • Frontiers Media SA  (6)
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Language
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  • 2020-2024  (6)
Year
  • 1
    Online Resource
    Online Resource
    DataSheet_4.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-5-26)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-26)
    Abstract: Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (T CM ) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (T EMRA ). Moreover, a virtual memory CD8+ T cell (T VM ) subset was enriched in CCL4-CCL5+ T EMRA cells and phenotypically distinctive from CCL4+ T CM subset, supported by single-cell RNA-Seq data. Specifically, T VM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ T CM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, T VM cells inhibited HIV-1 reactivation more effectively than non-T VM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting T VM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.897569
    DOI: 10.3389/fimmu.2022.897569.s001
    DOI: 10.3389/fimmu.2022.897569.s002
    DOI: 10.3389/fimmu.2022.897569.s003
    DOI: 10.3389/fimmu.2022.897569.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Data_Sheet_2.PDF
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-7-23)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-7-23)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.01541
    DOI: 10.3389/fimmu.2020.01541.s001
    DOI: 10.3389/fimmu.2020.01541.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-7)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-7)
    Abstract: Populations of natural killer cells lacking CD56 expression [CD56 neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood. Methods In this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56 neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56 neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined. Results The frequency of the CD56 neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56 neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56 dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56 neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56 neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56 neg NK cells and CD4 + T cell counts. Conclusions The results presented in this study indicate that the CD56 neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.811091
    DOI: 10.3389/fimmu.2021.811091.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-6-10)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-6-10)
    Abstract: Targeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8 + T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8 + T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8 + T-cell subsets in chronic HIV-1 infection remain poorly understood. Methods This study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8 + T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8 + T cells. Results The proportions of PD-1 + , CD39 + , and PD-1 + CD39 + CD8 + T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1 + CD39 + CD8 + T cells were negatively correlated with CD4 + T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39 + CD8 + T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39 - counterparts. In vitro , a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8 + T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells. Conclusion In patients with chronic HIV-1 infection there are increased frequencies of PD-1 + , CD39 + , and PD-1 + CD39 + CD8 + T cells. In treatment naïve patients, the frequencies of PD-1 + CD39 + CD8 + T cells are negatively correlated with CD4 + T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling in vitro may exert a synergistic effect in restoring CD8 + T-cell function in HIV-1-infected patients.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.687296
    DOI: 10.3389/fimmu.2021.687296.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-10-15)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-10-15)
    Abstract: Exhaustion of HIV-1-specific CD8 + T cells prevents optimal control of HIV-1 infection. Identifying unconventional CD8 + T cell subsets to effectively control HIV-1 replication is vital. In this study, the role of CD11c + CD8 + T cells during HIV-1 infection was evaluated. The frequencies of CD11c + CD8 + T cells significantly increased and were negatively correlated with viral load in HIV-1-infected treatment-naïve patients. HIV-1-specific cells were enriched more in CD11c + CD8 + T cells than in CD11c - CD8 + T cells, which could be induced by HIV-1-derived overlapping peptides, marking an HIV-1-specific CD8 + T cell population. This subset expressed higher levels of activating markers (CD38 and HLA-DR), cytotoxic markers (granzyme B, perforin, and CD107a), and cytokines (IL-2 and TNF-α), with lower levels of PD-1 compared to the CD11c - CD8 + T cell subset. In vitro analysis verified that CD11c + CD8 + T cells displayed a stronger HIV-1-specific killing capacity than the CD11c - counterparts. These findings indicate that CD11c + CD8 + T cells have potent immunotherapeutic efficacy in controlling HIV-1 infection.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.757457
    DOI: 10.3389/fimmu.2021.757457.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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    Online Resource
  • 6
    Online Resource
    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-12-20)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-12-20)
    Abstract: Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4 + T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4 + T cell aggregates in the peripheral blood of treatment-naïve HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4 + T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4 + T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4 + T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4 + T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4 + T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4 + T cell aggregates imply the potential role in CD4 + T cell loss during HIV-1 infection. Furthermore, platelet-CD4 + T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4 + T cell counterparts. The platelet-CD4 + T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4 + T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.799124
    DOI: 10.3389/fimmu.2021.799124.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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