The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface
The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface
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DOI：
10.1186/s12884-019-2218-6
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发表时间：
2019-02-19
影响因子：
3.1
通讯作者：
Szereday, Laszlo
中科院分区：
文献类型：
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作者：
Meggyes, Matyas;Miko, Eva;Szereday, Laszlo
BackgroundOur goal with this study is to investigate the contribution of PD-1/PD-L1 immune-checkpoint pathway to maternal immunotolerancemechanisms. Methods 13名健康孕妇和10名非妊娠对照参与了本项目。从外周血和蜕膜组织中分离PBMC和DIC。不同的免疫细胞亚群的表征后，我们使用荧光染料结合的单克隆抗体来测量PD-1，PD-L1，NKG 2D，和CD 107 a分子的表达水平通过流式细胞术。与外周血相比，还检测到蜕膜CD 8 + T、CD 4 + T和NKT样细胞的PD-1表达升高，同时蜕膜CD 4 + T、Treg、NKT样和CD 56 +NK细胞亚群的PD-L1表达增加。与外周相比，PD-1-蜕膜免疫细胞的细胞毒性潜力显著更高，然而，我们测量到与外周亚群相比，蜕膜PD-1+ CD 8 + T细胞的细胞毒性显著更低。与非妊娠条件相比，在妊娠早期，PD-1+ CD 8 + T亚群的活化受体NKG 2D表达降低，但与外周相比，蜕膜对应物的表达水平显著升高。蜕膜PD 1/NKG 2D双阳性CD 8 + T细胞的细胞毒性潜力显着降低相比，外周subsets.ConclusionsBased上我们的研究结果，我们假设PD-1/PD-L1通路可能有一个新的角色，在维持当地的免疫环境。通过与NKG 2D激活受体的相互作用，这种检查点相互作用可以调节蜕膜CD 8 Tc细胞亚群，并可能有助于母体免疫耐受。
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.