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Abstract
Trans-placental cell trafficking is a naturally occurring process during pregnancy that results in the direct recognition of foreign maternal antigens by fetal tissue and vice versa. Immigration of potentially harmful allo-reactive maternal T cells into fetal circulation may provoke anti-fetal immune responses. However, the contact with fetal tissue may favor differentiation of maternal immune cells into cells with a regulatory phenotype. Human Umbilical Vein Endothelial Cells (HUVECs) possess immune-regulating properties and are one of the first fetal cells to get in contact with foreign maternal immune cells. Therefore, here we studied whether HUVECs induce the conversion of maternal T cells into regulatory T (Treg) cells. Moreover, we assessed whether this response is changing according to the sex of the HUVECs. Both female and male HUVECs induced the conversion of maternal T cells into Treg cells which is partially mediated via TGF-β. Female HUVECs showed a stronger capacity to induce Treg cells compared to male HUVECs. Our findings propose that HUVECs contribute to fetal-maternal tolerance by the increase of the Treg cell population. Sex-specific differences in Treg cell induction may partly account for the disparities on the incidence of infectious and autoimmune diseases between both sexes during early childhood.
Highlights
Trans-placental cell trafficking is a naturally occurring process during pregnancy that results in the direct recognition of foreign maternal antigens by fetal tissue and vice versa
In the present study we identified Human Umbilical Vein Endothelial Cells (HUVECs) as inducers of Treg cells from maternal CD4+ T cells, at least in part through a TGF-β dependent pathway
We found primary female HUVECs to be more potent than primary male HUVECs in directing the maternal immune system
Summary
Trans-placental cell trafficking is a naturally occurring process during pregnancy that results in the direct recognition of foreign maternal antigens by fetal tissue and vice versa. It can be hypothesized that some of the immigrated maternal immune cells are allo-reactive, promote anti-fetal immune responses and have the potential of provoking fetal rejection. The contact with fetal antigens, may promote the differentiation of potential harmful maternal immune cells into fetus-friendly cells with a suppressive phenotype such as regulatory T (Treg) cells. Human Umbilical Vein Endothelial Cells (HUVECs) lining the wall of umbilical veins are very probably the first fetal cells getting in contact with immigrated maternal cells. This includes monocytes, natural killer cells, dendritic cells, T and B cells (reviewed in12,13) all detectable in cord blood. We further sought to elucidate whether HUVECs from female or male donors have different abilities in modulating the maternal immune system
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