Fetal–maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells

Abstract Human leukocyte antigen-C (HLA-C) is the only polymorphic classical histocompatibility antigen expressed by fetal trophoblasts at the fetal–maternal interface. Interactions between HLA-C and decidual natural killer (NK) cells may facilitate trophoblast invasion into maternal tissue. Thus far no evidence has been provided that decidual T cells specifically recognize and respond to fetal alloantigens at the fetal–maternal interface. In this study, we show that pregnancies containing a HLA-C mismatched child induce an increased percentage of CD4+ CD25dim activated T cells in decidual tissue. In addition, HLA-C mismatched pregnancies exhibit a decidual lymphocyte response to fetal cells and contain functional CD4+ CD25bright regulatory T cells in decidual tissue, whereas HLA-C matched pregnancies do not. This suggests that decidual T cells specifically recognize fetal HLA-C at the fetal–maternal interface but are prevented from inducing a destructive immune response in uncomplicated pregnancies.