Dynamics of effector and naïve Regulatory T cells throughout pregnancy

Regulatory T (Treg) cells are a specialized subset of T cells possessing immunosuppressive functions indispensable for the maintenance of self-tolerance and pregnancy. However, how functional Treg cells dynamically change and are engaged in feto-maternal tolerance during human pregnancy is still unclear. Recent studies have shown that functionally distinct and immunosuppressive subsets of Treg cells, i.e., effector Treg (eTreg) and naïve Treg (nTreg) cells, can be delineated by combinations of molecular markers and that their proportions differ in normal and disease states. In this study, we examined how the proportion of eTreg and nTreg cells in peripheral blood changes in the 1^st, 2^nd, and 3^rd trimesters of pregnancy and the postpartum period. During the 2^nd trimester the proportion of eTreg cells was reduced while nTreg cells was increased. This pattern was maintained throughout the 3^rd trimester of pregnancy. The kinetics of eTreg reduction highly correlated with migration of eTreg cells into feto-maternal interface while stable nTreg proportion paralleled with their expression of the anti-apoptotic molecule Bcl-2 and production of thymic emigrant naïve Treg cells. These results suggest that further studies on divergence of functional Treg proportions will be helpful for predicting instability of pregnancy.