Immune checkpoint molecules on T cell subsets of pregnancies with preeclampsia and gestational diabetes mellitus

Immune checkpoint molecules may play a crucial role in safeguarding pregnancy by regulating immune responses at the maternal-fetal interface. In this study, we aim to investigate the expression of PD-1, GITR, HLA-G, and CTLA-4 on T cell subsets in peripheral blood (PB), retroplacental blood (RPB), and cord blood (CB) in normal pregnancy (NP), preeclampsia (PE) and gestational diabetes mellitus (GDM). PB, RPB, and CB were collected immediately after delivery, and the expression of PD-1, GITR, HLA-G, and CTLA-4 on T cell subsets were measured by flow cytometric analysis. The proportions of Tregs in PB, RPB, and CB from NP were significantly higher than those of PE and GDM (P < 0.01, respectively). PD-1(+) and GITR(+) T cell subsets (CD3(+), CD4(+), and CD8(+) T cells, and Tregs) in PB, as well as PD-1(+) T cell subsets in RPB from NP, were significantly higher than those of PE and GDM (P < 0.01, respectively). In NP, PE, and GDM, the proportion of PD-1(+) Tregs was significantly decreased in CB as compared to those of PB and RPB (P < 0.05, respectively) and the proportion of GITR(+) Tregs was significantly higher in PB as compared to those of CB and RPB (P < 0.01, respectively). The proportion of HLA-G(+) Tregs in PB was significantly lower than those of CB and RPB (P < 0.01, respectively). In conclusion, decreased PD-1(+) and GITR(+) T cell subsets and decreased proportion of Tregs in PB and RPB may play a role in chronic inflammatory immune activation of effector T cells in PE and GDM.