Investigation of the PD-1 and PD-L1 Immune Checkpoint Molecules Throughout Healthy Human Pregnancy and in Nonpregnant Women

Abstract

Background: A growing body of evidence supports the importance of PD-1 and PD-L1, especially in the materno-fetal interface, although limited information is available about the peripheral expression of these molecules during the trimesters of pregnancy. Methods: 13 healthy women were enrolled from the 1st, 10 from the 2nd and 12 from the 3rd trimester of pregnancy at the same time, 10 healthy, age-matched nonpregnant women formed the control group. From peripheral blood, mononuclear cells were separated and stored at –80 °C. From freshly thawed samples, surface and intracellular staining were performed for flow cytometric analyses. CD107a degranulation assay was used to evaluate the cytotoxicity. Results: significant alternation was detected in PD-1 expression by CD8+T cells and in PD-L1 expression by CD8+T, CD4+T and Treg cells. An interesting relationship was revealed between the PD-1 and PD-L1 expression by the investigated subpopulations in 2nd trimester of pregnancy. Different expression patterns of an activation receptor NKG2D by the PD-1+ CD8+T cells was observed during pregnancy. The notable relationship was further determined in cytotoxicity between PD-1+ and NKG2D+ CD8+T cells throughout pregnancy. Conclusions: the different PD-1 presence and the relationship with NKG2D could contribute to the dynamic changes of the Th1 and Th2 predominance throughout the three trimesters of a healthy pregnancy.