Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints.

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre-eclampsia  are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid-derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications.

Expression level of immune checkpoint inhibitory factors in preeclampsia.

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation.