Successful pregnancy requires establishment of maternal immune tolerance to support embryo implantation and placental development. Regulatory T (Treg) cells are critical to this process, with reduced Treg cell abundance and/or function implicated in human pregnancy complications, however the mechanisms remain poorly defined. Here we investigate Treg cells in two separate clinical cohorts, a recurrent pregnancy loss (RPL) cohort and a spontaneous preterm labour (sPTL) cohort.
Treg cell deficiency has been reported in RPL, the underlying cause remains unknown. As insulin resistance is known to impair Treg cell function in other clinical settings, women (n=63) with at least two miscarriages underwent fasting blood sampling and an oral glucose tolerance test (OGTT) to assess glucose and insulin concentrations. Peripheral blood collected six weeks post-miscarriage was analysed by flow cytometry to characterise Treg cells, and linear regression was used to determine associations between metabolic parameters and immune phenotypes. Increasing fasting insulin, OGTT insulin, and insulin resistance were each associated with a reduction in activated, proliferating, immuno-suppressive memory Treg cell subsets, suggesting impaired Treg cell maturation and activation in RPL patients with metabolic dysfunction.
Treg cell deficiency has also been reported in women experiencing sPTL; however, previous studies have examined immune changes only after labour has commenced. To determine whether Treg cell abnormalities precede disease onset, cryopreserved blood T cells collected during early gestation from women who subsequently experienced sPTL (n=17) or uncomplicated term delivery (n=92) were analysed by flow cytometry. Women who delivered preterm exhibited reduced Treg cell frequency with altered phenotypes compared with women who delivered at term, demonstrating that immune dysregulation is evident months before the clinical onset of spontaneous preterm labour.
Together, these studies reinforce the critical role of maternal Treg cells during early pregnancy in establishing the immune environment required for successful pregnancy progression.