AUTHOR=Dai Xiao-Peng , Wu Feng-Ying , Cui Cheng , Liao Xue-Jiao , Jiao Yan-Mei , Zhang Chao , Song Jin-Wen , Fan Xing , Zhang Ji-Yuan , He Qing , Wang Fu-Sheng TITLE=Increased Platelet-CD4+ T Cell Aggregates Are Correlated With HIV-1 Permissiveness and CD4+ T Cell Loss JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.799124 DOI=10.3389/fimmu.2021.799124 ISSN=1664-3224 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.