Dynamic changes in regulatory T cells during normal pregnancy, recurrent pregnancy loss, and gestational diabetes

Abstract

Regulatory T cells (Tregs) are critical to regulating maternal T-cell activation against trophoblast; however, the characteristics of maternal Tregs during pregnancy have not been elucidated well. In this study, we analyzed the proportion of CD4+ and CD8+ Tregs in the peripheral blood and their surface expression of PD-1, GITR, HLA-G, and CTLA-4 in normal pregnant women during the first (n = 28), second (n = 43), and the third trimester (n = 33), non-pregnant women (n = 57), pregnant women with a history of recurrent pregnancy loss (RPL) during the first trimester (n = 21), and pregnant women with gestational diabetes mellitus (GDM) during the second (n = 17) and third trimester (n = 28). The proportions of CD4+ and CD8+ Tregs were higher in normal pregnant women than that of non-pregnant women (P < 0.01 respectively). The proportion of CD4+ Tregs was peaked during the second trimester and then decreased. Contrarily, the proportion of CD8+ Tregs was increased throughout gestation and peaked during the third trimester. Proportions of CD4+/PD-1+ Tregs, CD4+/GITR+ Tregs, CD8+/PD-1+ Tregs, and CD8+/CTLA-4+ Tregs peak during the third trimester of normal pregnancy. Pregnant women with RPL and GDM had lower proportions of CD4+ Tregs (P < 0.05 and P < 0.01 respectively) and higher proportions of CD8+ Tregs (P < 0.01 and P < 0.01 respectively) than those of normal pregnancies.Together, our findings indicate that CD4+ and CD8+ Tregs play different roles in pregnancy maintenance, and the dysregulation may contribute to obstetrical complications.