Expansion of CD4⁺HLA-G⁺ T cell in human pregnancy is impaired in pre-eclampsia

Problem: The role of CD4⁺HLA-G⁺ T cells in healthy pregnancy and pre-eclampsia is unclear. Method of study: CD4⁺HLA-G⁺ T cells were analysed from peripheral blood and decidual samples from healthy pregnant and pre-eclamptic women. In vitro T-cell induction, trogocytosis and suppression assays were performed. Results: In peripheral blood, CD4⁺HLA-G⁺ T cells were significantly higher in pregnant women (mean ± S.E.M.: 7.98 ± 1.10%), compared with non-pregnant controls (mean ± S.E.M.: 1.78 ± 0.30%) and pre-eclamptic women (mean ± S.E.M.: 3.69 ± 0.51%). The presence of CD4⁺HLA-G⁺ T cells is even more prominent in the decidua, suggestive of local induction and accumulation. Decidual CD14⁺DC-SIGN⁺ antigen-presenting cells (APCs) enhance the HLA-G expression of cocultured CD4⁺ naïve T cells in vitro. IL-10 augments expression of HLA-G, ILT4 and DC-SIGN in monocyte-derived DCs (MoDCs), endowing them with a phenotype analogous to decidual CD14⁺DC-SIGN⁺ APCs of healthy pregnancy. Furthermore, naïve T cells acquire HLA-G from these IL-10-treated MoDCs via the process of trogocytosis. Conclusions: Our data indicate that in addition to Foxp3⁺ Treg cells, CD4⁺ T cells acquire HLA-G from decidual DCs and may play an important role in immune tolerance induction in pregnancy, a process which is impaired in pre-eclampsia.