Regulatory T-cell phenotypes in prenatal psychological distress

Background: Experiencing symptoms of psychological distress during pregnancy is common and has been linked to dysregulated immune functioning. In this context, immunoregulatory function is especially relevant because of its crucial role in establishment and maintenance of healthy pregnancy. However, little research has examined associations between women's prenatal psychological distress and immunoregulatory biomarkers. We investigated how symptoms of depression, anxiety, and stress relate to circulating levels of regulatory T-cells (Tregs). Materials and methods: Pregnant Latina women were assessed at around 12 weeks of pregnancy (N = 82). These assessments included blood draws and self-report questionnaires assessing symptoms of depression, state anxiety, pregnancy-related anxiety, and perceived stress. Flow cytometry on PBMCs was used to quantify circulating Tregs, defined as CD3+CD4+CD25hiCD127loFoxP3+, and subpopulations positive for one of the following intraor extracellular markers, CD45RA, CTLA-4, Helios, PD-1, TIM-3, and TIGIT. We collected 82 samples at 12 weeks. Multivariable linear regressions tested for associations between symptoms of psychological distress and Treg concentrations, adjusted for gestational age. Results: State anxiety symptoms at 12 weeks were negatively associated with parent Treg cell levels (b = -4.02, p = 0.023) and subpopulations Helios+ (b = -3.29, p = 0.019) and TIM3+ (b = -3.17, p = 0.008). Perceived stress was negatively associated with the PD-1+ subpopulation at 12 weeks (b = -4.02, p = 0.023). Depression was not related to Tregs or the subpopulations. Conclusion: Our observation that symptoms of anxiety and stress are related to tolerogenic immunology suggests a possible biomechanism explaining correlations of maternal mood disorders with adverse outcomes for mothers and offspring.