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Increased Platelet-CD4⁺ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4⁺ T Cell Loss.

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.

SUBMITTER: Dai XP

PROVIDER: S-EPMC8720770 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHIV-2 infection is characterised by a longer asymptomatic phase and slower AIDS progression than HIV-1 infection. Identifying unique immune signatures associated with HIV-2 pathogenesis may thus provide therapeutically useful insight into the management of HIV infection. This study examined the dynamics of the CD4+T cell compartment, critical in disease progression, focussing on chronic HIV-2 and HIV-1 infected individuals at various stages of disease progression.MethodsA total of 111 participants including untreated and treated HIV infected individuals and seronegative individuals were enrolled in this study. The relative proportion of CD4+T cell subsets, expressing CD25 (IL-2R?) and CD127 (IL-7R), in HIV infected individuals and seronegative controls were assessed by multiparametric flow cytometry. Additionally, levels of immune activation and cytotoxic T lymphocytes in both the CD4+T and CD8+T cell compartments was evaluated.ResultsBoth treated and untreated, HIV-1 and HIV-2 infected individuals showed apparent dysregulation in CD4+ T cell subset frequency that was associated with disease progression. Furthermore, longitudinal sampling from a group of HIV-1 infected individuals on virologically effective ART showed no significant change in dysregulated CD4+T cell subset frequency. For both ART naïve and receiving groups associations with disease progression were strongest and significant with CD4+ T cell subset frequency compared to per cell expression of IL-2R? and IL-7R?. In untreated HIV-2 infected individuals, T cell activation was lower compared to ART naïve HIV-1 infected individuals and higher than seronegative individuals. Also, the level of Granzyme-B expressing circulating T cells was higher in both ART-naïve HIV-1 and HIV-2 infected individuals compared to seronegative controls.ConclusionDysregulation of IL-2 and IL-7 homeostasis persists in CD4+T cell subsets irrespective of presence or absence of viremia or antiretroviral therapy in HIV infection. Furthermore, we report for the first time on levels of circulating Granzyme-B expressing CD4+T and CD8+T cells in chronic HIV-2 infection. Lower immune activation in these individuals indicates that persistent immune activation driven CD4+T cell depletion, as observed in untreated HIV-1 infected individuals, may not be as severe and provides evidence for a disparate pathogenesis mechanism. Our work also supports novel immunomodulatory therapeutic strategies for both HIV-1 and HIV-2 infection.

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Increased Platelet-CD4⁺ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4⁺ T Cell Loss.

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OmicsDI is part of the ELIXIR infrastructure

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Increased Platelet-CD4+ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4+ T Cell Loss.

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OmicsDI is part of the ELIXIR infrastructure

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Increased Platelet-CD4⁺ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4⁺ T Cell Loss.