Altered Cytokine Production in Human Intervillous Blood T Cells in Preeclampsia

Conventional and regulatory T cells (Treg) are dynamic mediators of maternal immune tolerance to the developing feto-placental unit. Functional evaluation of T cells at the maternal-fetal interface is crucial to elucidate the immunologic basis of obstetric complications. Our objective was to define the T cell phenotype and function of uterine intervillous blood (IVB) in pregnancy with and without preeclampsia. We hypothesize that preeclampsia is associated with impaired immune tolerance and a pro-inflammatory uterine T cell microenvironment. In this cross-sectional study, maternal peripheral blood (PB) and uterine IVB (obtained from the surgical sponge used to clean the placental bed during cesarean delivery) were collected from participants with and without preeclampsia. Proportion, activation, and cytokine production of T cell subsets were quantified by flow cytometry. T cell parameters were compared by tissue source and by preeclampsia status. Sixty participants, 26 with preeclampsia, were included. Induced Treg made up a greater proportion of IVB T cells compared to PB and had greater cytokine-producing capacity. Preeclampsia was associated with increased ratio of pro-inflammatory IL-17α to suppressive IL-10 cytokine production by CD4 T cell subsets in IVB, but not in PB. Human uterine IVB is composed of activated, cytokine-producing T cell subsets distinct from maternal PB. Preeclampsia is associated with a pro-inflammatory IVB profile, with increased IL-17α /IL-10 ratio in all CD4 T cell subsets. IVB sampling is a useful tool for investigating human T cell biology at the maternal-fetal interface that may inform immunotherapeutic strategies for preeclampsia.