Transplacental immune programming refers to the concept that during pregnancy, significant crosstalk occurs between the maternal and fetal immune system, with consequent long?term effects especially for the offspring. In this study, we searched for evidence of transplacental programming in cellular immunity. We made the surprising observation that there is a stringent and specific correlation of regulatory T cells (Treg) between the mother and the fetus. Gene microarray analysis indicates that interleukin 10 (IL-10) might be involved in transplacental Treg alignment. This is further supported by the direct correlation of IL-10 at a protein level between maternal fetal dyads. In vitro data provide evidence that IL-10 may regulate the homeostatic balance between Tregs and non-Tregs through selective upregulation of the anti-apoptotic molecule Bcl-2 in Tregs. Induction of IL-10 might be triggered by fetus derived estriol (E3), which readily crosses the placenta and correlates with maternal IL- 10 levels. Our study represents the first example of transplacental regulation of cellular immunity between the mother and the fetus. These novel findings might have major implications for pregnancy related changes in the maternal and fetal immune system, and provide possible mechanistic insights into how prenatal influences can lead to subsequent immunopathologies, such as allergy and autoimmunity.

T-reg and non-Treg samples of non pregnant women, and matched cord blood and maternal blood T-regs and non-T-regs