The balance between cytotoxic NK cells and regulatory NK cells in human pregnancy

NK cells kill tumor cells and virus-infected cells as well as secrete a variety of cytokines. These effector functions are regulated by the balance between activating receptor signals and inhibitory receptor signals which are triggered by specific major histocompatibility complex (MHC) or non-MHC ligands. It is thought currently that the balance between immunostimulation and immunoregulation in T cell immunity is achieved by a Th1/Th2/Th3/Tr1 and CD4⁺CD25⁺ regulatory T (Treg) cell paradigm. Here, we discuss the cytokine paradigm of NK cells in human pregnancy. During normal, intact pregnancy, peripheral blood NKr1 cells and decidual NK3 cells increase, while these NK cell populations decrease significantly in miscarriage cases, suggesting that an imbalance in NK1/NK2/NK3/NKr1 is correlated with miscarriage. Recent investigations have shown that not only Treg cells, but also regulatory NK (NK reg) cells, play very important roles in the maintenance of pregnancy. We summarize the progress in studying NK reg cells and focus on how NK reg cells and cytotoxic NK cells affect the reproductive immune response.