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.