HLA-G and CD8+ regulatory T cells in the inflammatory environment of pre-eclampsia

During pregnancy, the maternal immune system is tolerant to foetal antigens via the engagement of immune regulatory mechanisms. Failure in regulating the maternal immunity to foetal antigens may lead to pre-eclampsia (PE). We addressed the role of HLA-G gene polymorphisms and protein expression as well as regulatory T cells and Th1/Th2/Th17 cytokines in healthy and pathological pregnancies. Blood samples from 26 pregnant women with PE, 25 non-PE and 7 strictly healthy pregnant women were assessed. PBMCs were phenotyped for early activation markers (CD25 and CD69), regulatory T-cell markers (CD8(+)CD28(-) and CD4(+)CD25(high)Foxp(3+)), ILT-2 (HLA-G receptor) and HLA-G. Lymphocyte proliferation was estimated and levels of IL-2, IL-4, IL-6, IL-10, IFN-gamma, TNF-alpha and IL-17 were measured. HLA-G polymorphisms (rs66554220 and rs1063320) were genotyped by PCR. PE women exhibited low levels of HLA-G in PBMCs and low frequency of regulatory CD8(+)CD28(-)T cells. High amounts of the pro-inflammatory cytokines IL-17, IL-2 and TNF-alpha as well as IL-4 and IL-10 and an increased proliferative cell activation profile were observed in PE. The allelic and genotypic frequencies of the HLA-G gene polymorphisms and the frequency of CD4(+)CD25(high)Foxp(3+) T cells did not vary among the groups. Our data suggest that the cytokine imbalance presented in PE is associated with a deficient immune regulatory profile, contributing to an impaired immune tolerance between mother and foetus.