Decidual and peripheral blood CD4 ⁺CD25 ⁺ regulatory T cells in early pregnancy subjects and spontaneous abortion cases

Human pregnancy represents a situation of semiallograft to maternal host. Therefore, it has been reported that tolerance to the fetal allograft represents a mechanism for maintaining a pregnancy. CD4 ⁺CD25 ^bright regulatory T cells are known to play an important role in the development and maintenance of tolerance in peripheral tissues. However, the potential role of CD4 ⁺CD25 ^bright T cells in maintaining human pregnancy has not been reported. In this study, we show that early human pregnancy decidua contains an abundance of CD4 ⁺CD25 ^bright T cells, which express CD152(CTLA-4 at a high level. CD4 ⁺CD25 ^bright T cells mediate potent inhibition of autologous T-cell proliferation by anti-CD3 stimulation. Furthermore, these cells inhibit the proliferation of autologous CD4 ⁺CD25 ^- T cells in a dose-dependent fashion. This suppressive function of decidual CD4 ⁺CD25 ⁺ T cells required cell-to-cell contact. The proportion of decidual CD4 ⁺CD25 ^bright T cells was significantly lower in specimens from spontaneous abortion compared to those from specimens from induced abortions. These results suggest that decidual CD4 ⁺CD25 ^bright T cells contribute to the mechanisms mediating maternal immune tolerance of conceptus antigens and therefore might contribute to the maintenance of pregnancy.