The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface.

BACKGROUND: Our goal with this study was to investigate the contribution of PD-1/PD-L1 immune-checkpoint pathway to maternal immunotolerance mechanisms. METHODS: Thirteen healthy pregnant women and 10 non-pregnant controls were involved in this project. PBMCs and DICs were isolated from peripheral blood and from decidual tissues. After the characterization of different immune cell subsets, we used fluorochrome-conjugated monoclonal antibodies to measure the expression level of PD-1, PD-L1, NKG2D, and CD107a molecules by flow cytometry. RESULTS: We measured significant alternations in the proportion of decidual immune cell subsets compared to the periphery. Elevated PD-1 expression by decidual CD8+ T, CD4+ T, and NKT-like cells were also detected accompanied by the increased PD-L1 expression by decidual CD4+ T, Treg, NKT-like and CD56 + NK cell subsets compared to peripheral blood. The cytotoxic potential was significantly higher in PD-1- decidual immune cells compared to the periphery, however we measured a significantly lower cytotoxicity in the decidual PD-1+ CD8+ T cells compared with the peripheral subsets. An activation receptor NKG2D expression was decreased by the PD-1+ CD8+ T subsets in the first trimester compared to non-pregnant condition but the expression level of the decidual counterparts was significantly elevated compared to the periphery. The cytotoxic potential of decidual PD1/NKG2D double positive CD8+ T cells was significantly decreased compared to the peripheral subsets. CONCLUSIONS: Based on our results we assume that PD-1/PD-L1 pathway might have a novel role in the maintaining of the local immunological environment. Accompanied by NKG2D activating receptor this checkpoint interaction could regulate decidual CD8 Tc cell subsets and may contribute maternal immunotolerance.

Investigation of mucosal-associated invariant T (MAIT) cells expressing immune checkpoint receptors (TIGIT and CD226) in early-onset preeclampsia.

OBJECTIVE: During our work, we examined the possible contribution of MAIT cells in the pathogenesis of the clinical phase of early-onset preeclampsia and how this could be influenced by TIGIT and CD226 immune checkpoint molecules. STUDY DESIGN: 37 pregnant women diagnosed with early-onset preeclampsia and 36 healthy, age-matched control women were involved in this study. Peripheral blood mononuclear cells were isolated by density gradient and frozen. After thawing, cells were stained with monoclonal antibodies to characterize MAIT, MAIT-like, and non-MAIT cells. Flow cytometric analyses were used to measure TIGIT, CD226, intracellular perforin, and granzyme B expression. RESULTS: MAIT (CD3+ CD8+ Vα7.2+ CD161++), MAIT-like (CD3+ CD8+ Vα7.2+ CD161+) and non-MAIT (CD3+ CD8+ Vα7.2+ CD161-) cell population were identified based on their CD161 receptor positivity. MAIT cells markedly differed in proportion, TIGIT expression, granzyme B, and perforin content compared to MAIT-like and non-MAIT cells. A significant difference was determined in TIGIT expression by non-MAIT cells and in CD8/CD226 positive relationship between the preeclamptic and healthy condition. CONCLUSIONS: Considering that we did not detect a notable difference between early-onset preeclampsia and healthy pregnancy, we suppose that peripheral MAIT cells expressing TIGIT and CD226 immune checkpoint molecules have a marginal role in the pathogenesis of early-onset preeclampsia.