Maternal-fetal HLA compatibility and trophoblast-immune interactions in healthy and preeclamptic pregnancy: elegance in complexity

Hof, L.J. van 't

Pregnancy represents a striking immunological paradox: the maternal immune system must maintain tolerance toward the semi-allogeneic fetus while preserving effective protection against infections. Understanding the mechanisms that enable this balance is key to unraveling the pathogenesis of severe immune-mediated complications such as preeclampsia.
This dissertation investigates the pathways by which maternal-fetal tolerance is established and how these are disrupted in preeclampsia, with a particular focus on maternal-fetal HLA compatibility and trophoblast-mediated modulation of maternal CD4+ T cell responses.
Population-based genetic analyses assess the role of maternal-fetal HLA compatibility, the contribution of HLA mismatches to immune regulation and its link to hypertensive pregnancy disorders. In addition, the feasibility of early non-invasive fetal HLA typing is evaluated by isolating extravillous trophoblasts from maternal cervical samples....Show morePregnancy represents a striking immunological paradox: the maternal immune system must maintain tolerance toward the semi-allogeneic fetus while preserving effective protection against infections. Understanding the mechanisms that enable this balance is key to unraveling the pathogenesis of severe immune-mediated complications such as preeclampsia.
This dissertation investigates the pathways by which maternal-fetal tolerance is established and how these are disrupted in preeclampsia, with a particular focus on maternal-fetal HLA compatibility and trophoblast-mediated modulation of maternal CD4+ T cell responses.
Population-based genetic analyses assess the role of maternal-fetal HLA compatibility, the contribution of HLA mismatches to immune regulation and its link to hypertensive pregnancy disorders. In addition, the feasibility of early non-invasive fetal HLA typing is evaluated by isolating extravillous trophoblasts from maternal cervical samples. Furthermore, this work characterizes key immunomodulatory molecules in placental tissue from naturally conceived and oocyte donation pregnancies, with and without preeclampsia. Using an in vitro co-culture model of trophoblasts and conventional CD4+ T cells, the induction of regulatory T cell features is explored.
Collectively, this dissertation provides insight into the crucial regulating mechanisms of maternal–fetal immune interactions and identifies immunological factors that may serve as future targets for the prediction, prevention, or treatment of preeclampsia.Show less

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Maternal-fetal HLA compatibility and trophoblast-immune interactions in healthy and preeclamptic pregnancy: elegance in complexity