The role of γδ-T cells during human pregnancy

Pregnancy is an evolutionarily important and mysterious process. The placenta, as the nutrient and gas exchange organ, plays an essential role during this process. In addition, the interaction between trophoblast and maternal immune cells at the maternal-fetal interface is also associated with successful pregnancy. Human leukocyte antigen (HLA) molecules on trophoblast cells are involved in protecting the fetus from maternal rejection. Trophoblast cells comprise three subpopulations, including syncytiotrophoblast cells, cytotrophoblast cells, and extravillous trophoblast cells, and these cells express different HLA molecules. Syncytiotrophoblast and extravillous trophoblast cells encounter maternal immune cells from different sources, such as blood or decidua. The increased γδ-T cells during human normal pregnancy indicate that these cells may play a role in this process. In peripheral blood, Vγ9Vδ2-T cells display cytotoxicity through the recognition of phosphoantigens derived from pathogens. However, HLA-E molecules protect the trophoblast cells from the cytotoxicity of Vγ9Vδ2-T cells through binding to the inhibitory receptor, CD94/NKG2A. In decidua, the main Vδ1-T cells maintain the pregnancy through the secretion of cytokines. In addition, the imbalance between Vγ9Vδ2-T and Vδ1-T cells, and the abnormal expression of the receptors on γδ-T cells were observed in adverse pregnancy.