The effect of human placenta cytotrophoblast cells on the maturation and T cell stimulating ability of dendritic cellsin vitro

Abstract

SummaryThe success of pregnancy depends upon regulatory mechanisms that allow the fetus to survive and develop to term in the uterus, despite maternal immune cells' awareness of paternal alloantigens. At least some of these specific mechanisms are mediated by the effect of fetal trophoblast cells. In the present study we examine the effect of human placental cytotrophoblast cells (CTCs) on the maturation of dendritic cells (DCs) in vitro. For that purpose, CTCs were isolated from samples of placentae at 5-11 weeks of gestation and co-cultured with peripheral blood monocytes under conditions inducing DC maturation. CTC were shown to alter the morphology, phenotype and functional properties of DCs. As a result, a significant portion of cells acquire fibroblast-like morphology and some of the cells retain the expression of CD14. DCs matured in the presence of CTCs do not differ from usual DCs in terms of CD80, CD83 and CD86 expression, as well as the ability to induce allogenic lymphocytes proliferation. However, CTCs reduce significantly the ability of DCs to stimulate interferon-g production and the loss of CD62L by T cells. The results obtained indicate that DCs may be involved in pregnancyassociated changes of cytokine production and T cell migration.

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

“…CD14 is often considered a marker of macrophages, with which dendritic cells are closely related. It has, however, been shown that CD14 expression is retained in dendritic cells when they develop in the presence of trophoblasts (Talayev et al 2010). These facts, together with the source of cells in this experiment, suggest that these are uterine dendritic cells and thus of maternal origin (Kammerer et al 2000;Tagliani and Erlebacher 2011).…”

“…These cells lack expression of CD19, CD209, and CD163 but express the combination of markers ITGAX + / CD14 + /CD4 + /CD83 + / CD86 + . The genes CLEC4C, THBD, CD1C, CD80, IL10, and IL12B that characterize some of the decidual DCs (Kammerer et al 2008;Talayev et al 2010) were not found. CD14 is often considered a marker of macrophages, with which dendritic cells are closely related.…”

Immune Modulatory Effects of Human Chorionic Gonadotropin on Dendritic Cells Supporting Fetal Survival in Murine Pregnancy

“…Several human and murine studies proposed trophoblast-associated factors as potential candidates in DC modulation (9, 10). This includes factors, such as soluble thymic stromal lymphopoitin and pregnancy-specific glycoprotein (11, 12).…”

Leptin and ghrelin regulate dendritic cell maturation and dendritic cell induction of regulatory T-cells

“…A suspension of peripheral blood mononuclear cells (PBMCs) was isolated by the centrifugation in a ficoll-verografin density gradient (1.077 g/cm 3 ). DCs were generated by the standard method [5]. PBMCs (1-5 × 10 6 cells/mL) were resuspended in a complete nutrition media (CNM; RPMI 1640 supplemented with 10% fetal calf serum, 1 mM HEPES, 2 mM L glutamin, and 100 μg/mL streptomycin), then plated on 24 well polystyrene plates (Costar, United States), 2 mL per well, and cultured for 3 h at 37°C and 5% CO 2 .…”

“…Physiologic saline used for dissolving the hormones was added to the control samples. Granulocyte-macrophage colony stimulating factor (GM CSF) (100 ng/mL, R&D, United States) and IL 4 (20 ng/mL, BioLegend, United States) were added for the induction of DC formation in the sam ples [5]. The cells were incubated at 37°C and 5% CO 2 for 5 days.…”