The Role of the PD-1 Immunoreceptor in Pregnancy

Abstract

During pregnancy, the maternal immune system must be carefully modulated as the fetus is immunologically foreign to her leukocytes. We propose that the CD28 family immune receptor, PD-1, functions during pregnancy to control maternal immune reactions. PD-1 is expressed on T lymphocytes and following interaction with its ligand, B7-H1, prevents T cell activation. B7-H1 is expressed in the human placenta throughout gestation, therefore we studied the role of the PD-1 receptor in modulating maternal T cells during pregnancy. PD-1 is preferentially expressed on human decidual T cells and B7-H1 inhibits the inflammatory cytokine production of activated decidual T lymphocytes. In addition, possibly through B7-H1:PD-1 interactions, trophoblasts induce regulatory T cell expansion in vitro. Finally, in murine pregnancy, PD-1 controls the accumulation of paternal antigen-specific T cells in the uterus-draining lymph nodes. Overall, these studies suggest that the PD-1:B7-H1 pathway functions to help maintain maternal-fetal tolerance.