Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage

Abstract

The development of pregnancy is possible due to initiation of immune response in the body of the mother resulting in immune tolerance. Miscarriage may be caused by the impaired maternal immune response to paternal alloantigens located on the surface of trophoblast and fetal cells. The aim of the study was to compare the population of circulating dendritic cells (DCs) and CD4+CD25+Foxp3+ regulatory T cells (TREGs) in the first trimester of a normal pregnancy and in women with recurrent miscarriage and an attempt to determine the relationship between these cells and the role they may play in human reproductive failures. The study was conducted in a group of 33 first trimester pregnant women with recurrent miscarriage and in a group of 20 healthy pregnant women in the first trimester of normal pregnancy. Among mononuclear cells isolated from peripheral blood, the populations of DCs and TREGs were assessed by flow cytometry. The percentage of myeloid DCs and lymphoid DCs showed no significant difference between study and control group. Older maternal age and obesity significantly reduced the pool of circulating myeloid and lymphoid DCs (R=-0.39, p=0.02). In miscarriages the percentage of circulating TREGs was significantly lower compared to normal pregnancies (p=0.003). Among the analysed factors the percentage of TREGs was the most sensitive and the most specific parameter which correlated with the pregnancy loss. The reduction in the population of circulating TREGs suggests immunoregulatory mechanisms disorder in a pregnancy complicated by miscarriage.

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

“…In addition, the progesterone–HO‐1 system reduced the expansion of cytotoxic CD8 + T cells that recognize non‐self antigens expressed by the embryo . Consistently, a correlation was shown for pregnant women between current miscarriage and a reduced amount of regulatory T cells, despite having regular numbers of circulating DCs . These data suggest that HO‐1 regulates DC activity and the capacity to induce T‐cell‐mediated tolerance.…”

“…132 Consistently, a correlation was shown for pregnant women between current miscarriage and a reduced amount of regulatory T cells, despite having regular numbers of circulating DCs. 133 These data suggest that HO-1 regulates DC activity and the capacity to induce T-cell-mediated tolerance.…”

LPS-treated bone marrow-derived dendritic cells induce immune tolerance through modulating differentiation of CD4+ regulatory T cell subpopulations mediated by 3G11 and CD127

“…Multiple specific markers of T regs have been found after T regs were reported in 1990s [24–27]. It has been known that phenotype of conventional T regs is CD4 + CD25 + FoxP3 + T cells [11, 28]. Moreover, GITR is also expressed on surface of typical CD4 + T regs [13].…”

What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages?

“…Women with RM having low CD4+CD25+Foxp3+ Treg levels in the first trimester experienced a significantly lower ongoing pregnancy rate than those with a higher Treg level in the first trimester . The decreased expansion of Tregs during pregnancy in the unexplained RM group may predispose to pregnancy loss, and Tregs might serve as a pregnancy marker to aid in predicting miscarriage risk in newly pregnant women . Furthermore, this highlights the opportunity to use Treg therapy to increase the success rate in women who repeatedly experience pregnancy losses.…”