Abstract
BackgroundOur goal with this study was to investigate the contribution of PD-1/PD-L1 immune-checkpoint pathway to maternal immunotolerance mechanisms.MethodsThirteen 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.ResultsWe 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.ConclusionsBased 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.
Highlights
Our goal with this study was to investigate the contribution of Programmed cell death protein 1 (PD-1)/Programmed cell death ligand-1 (PD-L1) immune-checkpoint pathway to maternal immunotolerance mechanisms
To our findings many papers previously reported that the ratio of decidual CD56 + Natural killer cells (NK) cells and CD56dimNK and CD56brightNK cell subsets were significantly elevated compared to the periphery (Table 1)
In the case of the Treg subpopulation, we further detected a significantly increased PD-L1 expression in the 1st-trimester of pregnancy compared to the non-pregnant group (Fig. 3b)
Summary
Our goal with this study was to investigate the contribution of PD-1/PD-L1 immune-checkpoint pathway to maternal immunotolerance mechanisms. Pregnancy is a useful model to investigate natural immunotolerance since the semi-allogeneic fetus will neither be attacked nor rejected by the maternal immune system, but rather successfully accepted by the mother. A healthy pregnancy requires that the maternal immune system recognizes the antigens from paternal origin expressed by the fetus thereby developing maternal immunotolerance against the fetus. As a co-inhibitory molecule PD-1 is expressed by a variety of activated immune cells, including T (CD4+, CD8+, NKT-like and regulatory T (Treg)) cells, B cells, monocytes and dendritic cells [5, 6]. The Meggyes et al BMC Pregnancy and Childbirth (2019) 19:74 receptor expression could be rapidly up-regulated within 24 h by naive T cells [7]. The receptor has been originally identified on exhausted T cells, and in most cases the blockade of PD-1 signaling has been shown to revert the dysfunctional state of exhausted CD8+ T cells [8, 9]
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