BackgroundThis study aimed to test the hypothesis that immune dysfunction and the increased risk of spontaneous abortion in pregnant women with hyperandrogenia (HA) are caused by the reduced tolerogenic potential of dendritic cells (DCs) that results from elevated levels of dehydroepiandrosterone sulfate (DHEAS).MethodsThe phenotypic and functional properties of monocyte-derived DCs generated from blood monocytes from non-pregnant women, women with a normal pregnancy, or pregnant women with HA, as well as the in vitro effects of DHEAS on DCs in healthy pregnant women were investigated.ResultsIn a normal pregnancy, DCs were shown to be immature and are characterized by a reduced number of CD83+ and CD25+ DCs, the ability to stimulate type 2 T cell responses and to induce T cell apoptosis. By contrast, DCs from pregnant women with HA had a mature phenotype, were able to stimulate both type 1 (IFN-γ) and type 2 (IL-4) T cell responses, and were characterized by lower B7-H1 expression and cytotoxic activity against CD8+ T cells. The addition of DHEAS to cultures of DCs from healthy pregnant women induced the maturation of DCs and increased their ability to activate type 1 T cell responses.ConclusionOur data demonstrated the reduction in the tolerogenic potential of DCs from pregnant women with HA, and revealed new mechanisms involved in the hormonal regulation of DCs mediated by DHEAS.

The aim of the study was to evaluate FoxP3+ regulatory T cell (Тreg) subsets in the follicular fluid (FF) of the women undergoing in vitro fertilization (IVF), and their relationships with features of folliculogenesis and oogenesis, as well as quality of embryos and retrospective assessment of IVF outcomes. The study included 53 women at the age of 25 to 46 years stimulated by superovulation. The count of Tregs in the FF samples was determined by flow cytometry using appropriate monoclonal antibodies. The FF examination revealed of FoxP3+ T cells from both CD4+ (CD4+FoxP3+) and CD4(CD4-FoxP3+) T lymphocyte subsets. Moreover, the FoxP3+ cells were registered in CD4+CD25+ and CD4+CD25T lymphocyte subsets. Follicular fluid of women with a relatively small number of follicles contained higher numbers of CD4+CD25-FoxP3+ T cells, whereas a reduced number of oocytes was associated with the highest count of CD4-FoxP3+ T cells in FF. Retrospective analysis showed the a relationship between percentage of Tregs, and quality of oocytes and embryos. High fertilization index (0.75-1.0), reflecting maturity of the oocytes was associated with higher count of CD4-FoxP3+ T cells in the FF. Better quality of blastocysts was associated with a higher count of both CD4-FoxP3+ and CD4+FoxP3+ T cells. Onset and progression of pregnancies was also registered in women with relatively high counts of CD4-FoxP3+ T cells. The obtained data showed presence of different FoxP3+ T cell subtypes in follicular fluid, and its possible role in controlling early stages of reproductive process. CD4-FoxP3+ T cells seem to be the most important subpopulation; their counts are associated with efficacy of oogenesis, blastulation and pregnancy occurence.

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Background. Inhibitory receptors and their ligands (also called checkpoint molecules) are important feedback regulators of the immune response. However, their role in immunological adaptation during pregnancy remains poorly understood.The aim of the study was to evaluate the level of checkpoint molecule (PD-1, CTLA-4, Tim-3) expression in peripheral T cells in pregnant women compared with fertile non-pregnant women.Materials and methods. The study included 36 women in the second half of pregnancy without pregnancy complications, 12 of whom had extragenital pathology. The control group consisted of 28 age-matched fertile non-pregnant women. The proportion of CD8+PD-1+, CD8+TIM-3+, CD8+PD-1+TIM-3+, CD4+PD-1+, CD4+TIM-3+, and CD4+PD-1+TIM-3+ was evaluated by flow cytometry using the corresponding monoclonal antibodies (BD Biosciences, USA).Results. The proportion of CD4+Tim-3+ and CD8+PD-1+ Т cells and CD4+ and CD8+ Т lymphocytes co-expressing PD-1 and Tim-3 in the peripheral blood of pregnant women was statistically significantly higher than in non-pregnant women. An increase in CD4+Tim-3+ and CD8+PD-1+ T cells was observed both in pregnant women with and without extragenital pathology. However, pregnant women with extragenital pathology were characterized by a higher CD8+PD-1+ count and a smaller number of CD8+Tim-3+ cells, as well as by a lack of an increase in PD-1+Tim-3+ T cells typical of pregnant women. The number of comorbidities was directly correlated with the proportion of CD8+PD-1+ lymphocytes and inversely correlated with the proportion of CD8+Tim-3+ and CD4+ PD-1+Tim-3+ cells. In addition, the expression of checkpoint molecules was associated with gestational age (a direct correlation was found with the proportion of CD8+Tim-3+, CD4+PD-1+Tim-3+, and CD8+PD-1+Tim-3+ cells) and to a lesser extent – with the age of pregnant women (an inverse relationship was found with the proportion of CD8+Tim-3+ cells).Conclusion. Pregnant women in the second half of pregnancy are characterized by increased expression of PD-1 and Tim-3 molecules in peripheral T cells. At the same time, concomitant extragenital pathology affects the expression of these molecules.