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

The 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-γ production and the loss of CD62L by T cells. The results obtained indicate that DCs may be involved in pregnancy-associated changes of cytokine production and T cell migration.

Ex vivo stimulation of cord blood mononuclear cells by dexamethasone and interleukin-7 results in the maturation of interferon-gamma-secreting effector memory T cells.

The effects of dexamethasone phosphate and interleukin-7 upon the proliferation of T-cells and the production of interferon-gamma in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T-cell proliferation induced by anti-CD3 with interleukin-7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon-gamma in 68-h cell cultures stimulated with anti-CD3 both in the presence of interleukin-7 and without it. However, a 68-h cultivation of newborn blood cells with dexamethasone, anti-CD3 and interleukin-7 resulted in the accumulation of T-lymphocytes capable of producing interferon-gamma after restimulation. As a result of it the amount of interferon-gamma producing CD7(+) T-cells and the concentration of interferon-gamma in cultural supernatants were maximal in the cell cultures incubated with anti-CD3, interleukin-7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12-myristate 13-acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti-CD3 and interleukine-7 also causes a decrease in the number of naïve T-cells and central memory cells and an increase in the number of effector memory CD7(+)CD45RA(+)CD62L(-) cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL-7 receptor expression: it is known that IL-7 receptor alpha-chain gene is a glucocorticoid-inducible gene.