Medical School of Chinese People's Liberation Army of China (PLA), Beijing, China.
Noncommissioned Officer School, Army Medical University, Shijiazhuang, China.
Front Immunol. 2021 Dec 20;12:799124. doi: 10.3389/fimmu.2021.799124. eCollection 2021.
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.
慢性 HIV-1 感染与持续的炎症有关,炎症会促进疾病进展。血小板-T 细胞聚集体在维持炎症中起着关键作用。然而,在不同的 HIV 感染人群中,血小板-CD4 T 细胞聚集体的表型特征和临床意义尚不清楚。在这项研究中,我们定量和表征了治疗初治 HIV-1 感染个体(TNs)、抗逆转录病毒治疗免疫应答者(IRs)、抗逆转录病毒治疗免疫无应答者(INRs)和健康对照者(HCs)外周血中的血小板-CD4 T 细胞聚集体。流式细胞术分析和免疫荧光显微镜显示,在 HIV-1 感染期间,TNs 中血小板-CD4 T 细胞聚集体的形成增加。然而,与 TNs 相比,IRs 中血小板-CD4 T 细胞聚集体的频率降低,但 INR 中没有降低,而 INR 表现出严重的免疫功能障碍。血小板-CD4 T 细胞聚集体的频率与 HIV-1 病毒载量呈正相关,与 CD4 T 细胞计数和 CD4/CD8 比值呈负相关。此外,我们观察到血小板-CD4 T 细胞聚集体中 CD45RO、HIV 共受体、HIV 激活/耗竭标志物的表达更高,这与 HIV-1 的易感性有关。血小板-CD4 T 细胞聚集体中 caspase-1 和 caspase-3 水平较高,Bcl-2 水平较低,这意味着它们在 HIV-1 感染过程中可能导致 CD4 T 细胞的丢失。此外,血小板-CD4 T 细胞聚集体中含有比其无血小板-CD4 T 细胞聚集体更多的 HIV-1 gag 病毒蛋白和 HIV-1 DNA。血小板-CD4 T 细胞聚集体的水平与血浆 sCD163 和 sCD14 水平呈正相关。我们的研究结果表明,血小板-CD4 T 细胞聚集体的形成具有 HIV-1 易感性的典型特征,并与 HIV-1 感染期间的免疫激活有关。