Recent Insight into the Role of the PD-1/PD-L1 Pathway in Feto-Maternal Tolerance and Pregnancy

Pregnancy presents a great challenge to the maternal immune system. Given that maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to serve a central function in altering the maternal immune responses. Regulatory T cells (Tregs) and the PD-1/PD-L1 pathway are both critical in controlling the immune responses. Recent studies have proved the critical function of the PD-1/PD-L1 pathway in regulating the T-cell homeostasis and the peripheral tolerance through promoting the development and function of Tregs, and inhibiting the activation of effector T cells. The function of the PD-1/PD-L1 pathway in feto-maternal interface and pregnancy has been investigated in human and animal models of pregnancy. In this review, we provide recent insight into the role of the PD-1/PD-L1 pathway in regulating T-cell homeostasis, maternal tolerance, and pregnancy-related complications as well as its possible applicability in clinical immunotherapy.