Maternal immune activation alters basal T-cell maturation, activation, and regulation as well as basal monocyte activation and responsiveness to stimulation of HEU infants at birth

This study assessed whether maternal HIV status and cytokine/chemokine profiles impact infant growth, T-cell and monocyte activation, regulation, and monocyte responsiveness to stimulation at birth and early infancy. A total of 148 pregnant women – 71 pregnant women/mothers living with HIV (MLWH) and 77 without HIV – were recruited at 22 weeks’ gestation and followed until 12 months postpartum. Bloods were drawn from mothers at 28 weeks’ gestation and birth, and from infants at birth, six-, 10 and 14 weeks, and six months. This study is one of several multi-disciplinary sub-studies forming part of a larger umbrella study called the Siyakhula study. The Siyakhula study is a prospective, longitudinal, descriptive cohort study initiated in 2018 by clinicians and researchers at the University of Pretoria (UP), Pretoria, SA. The Siyakhula study recruited a cohort of 315 dyads (152 pregnant women living with HIV [PWLWH] and their HIV-exposed-uninfected [HEU] infants and 163 pregnant women not living with HIV [PWNLWH] and their HIV-unexposed-uninfected [HUU] infants) from antenatal clinics in Southwest Tshwane, SA, at less than 22 weeks’ gestation. Follow-up visits occurred at 28- and 36-weeks’ gestation; birth; six-, 10-, 14- and 24-weeks; and one- and two-years of age. Two sets of data were acquired from two separate subsets of samples from the Siyakhula cohort on two different flow cytometry systems with slightly different antibody panels for each cell subset. These included: one to characterise and quantify CD4+ and CD8+ T-cell subsets; one to detect and quantify the presence of regulatory T-cells (Tregs); as well as a third panel to characterise the activation status of monocytes/macrophages. All the multi-parameter flow cytometry results are depicted separately for each data set (Cohort 1 = Becton Dickenson [BD] analysed cohort; Cohort 2 = CytoFlex analysed cohort, Cohort 3 = combined analysis of Cohorts 1 and 2) at each time point investigated. Whole blood stimulation assays were performed to assess monocyte/macrophage responsiveness in HEU and HUU infants at birth, 10 weeks, and six months of age with the TLR agonists, lipopolysaccharide (LPS) and polyinocinic-polycytidylic acid (PolyI:C).The pro- and anti-inflammatory cytokine/chemokine profiles were charaterised in MLWH and MNLWH at 28 weeks’ gestation and in HEU and HUU infants at 10 weeks, and six months of age. Pro-inflammatory responses were characterised by increased levels of granulocyte/macrophage-colony stimulating factor (GM-CSF), IFN-γ, IL-2, IL-6, IL-8, and TNF-α. Anti-inflammatory responses, in turn, were characterised by increased expression of IL-4, IL-10 and TGF-β1.Data presented here include the demographic information and anthropometric data compared at the various time points for all the mothers and their infants, the flow cytometry results for the CD4+, CD8+ and regulatory T-cells (Tregs), as well as the monocyte subsets compared between MLWH and MNLWH as well as HEU and HUU infants, the results of whole blood stimulation (WBS), cytokine/chemokine, transforming growth factor (TGF)-β, soluble cluster of differentiation (CD)14 (sCD14), neopterin and C-reactive protein (CRP) concentrations.

本研究旨在评估母亲HIV感染状态及细胞因子/趋化因子谱对婴儿生长发育、T细胞和单核细胞激活、调节以及单核细胞对出生及早期婴儿期刺激的反应性的影响。共招募了148名孕妇——其中71名HIV阳性孕妇/母亲（MLWH）和77名HIV阴性孕妇——在妊娠22周时进行招募，并一直跟踪至产后12个月。在妊娠28周和分娩时，从母亲体内抽取血液，从婴儿出生时、6周、10周、14周及6个月大时抽取血液。本研究是多个跨学科子研究之一，这些子研究构成了一个名为Siyakhula的大型研究框架的一部分。Siyakhula研究是由南非比勒陀利亚大学（UP）的医生和研究人员于2018年启动的一项前瞻性、纵向、描述性队列研究。Siyakhula研究在南非西南部Tshwane的产前诊所招募了315对（152名HIV阳性孕妇（PWLWH）及其HIV暴露未感染（HEU）婴儿和163名HIV阴性孕妇（PWNLWH）及其HIV未暴露未感染（HUU）婴儿）在妊娠不足22周时进行招募。随访访问发生在妊娠28周和36周、分娩、6周、10周、14周和24周，以及1岁和2岁时。从Siyakhula队列的两个独立样本子集中，使用两种不同的流式细胞术系统以及针对每个细胞亚群略有不同的抗体面板，收集了两套数据。这些数据包括：一套用于表征和量化CD4+和CD8+ T细胞亚群；一套用于检测和量化调节性T细胞（Tregs）的存在；以及第三套用于表征单核细胞/巨噬细胞的活化状态。所有多参数流式细胞术结果在每个研究时间点分别描述（队列1=贝克顿·迪金森[BD]分析的队列；队列2=CytoFlex分析的队列；队列3=队列1和2的联合分析）。对HEU和HUU婴儿在出生时、10周和6个月大时使用TLR激动剂、脂多糖（LPS）和聚肌苷酸-聚胞苷酸（PolyI:C）进行全血刺激试验，以评估单核细胞/巨噬细胞的反应性。在MLWH和MNLWH妊娠28周、HEU和HUU婴儿10周和6个月大时，对促炎和抗炎细胞因子/趋化因子谱进行了表征。促炎反应的特征是粒细胞/巨噬细胞集落刺激因子（GM-CSF）、干扰素-γ、IL-2、IL-6、IL-8和TNF-α水平升高。相反，抗炎反应的特征是IL-4、IL-10和TGF-β1表达增加。本研究所呈现的数据包括所有母亲及其婴儿在不同时间点的流行病学信息和体格测量数据、CD4+、CD8+和调节性T细胞（Tregs）的流式细胞术结果，以及MLWH和MNLWH以及HEU和HUU婴儿之间单核细胞亚群的比较，全血刺激（WBS）结果，细胞因子/趋化因子、转化生长因子（TGF）-β、可溶性Cluster of Differentiation 14（sCD14）、新蝶呤和C反应蛋白（CRP）浓度。