Disruption of maternal tolerance during pregnancy leads to Treg repopulation of the antigenic UPI (BA13P.123)

Abstract

Background Regulatory T cells (Treg) are essential for normal pregnancy outcome. In vivo, Treg depletion during pregnancy leads to autoimmunity that results in total pregnancy loss. The paucity of Treg and effector cells in normal pregnancy uteroplacental interfaces (UPI) renders the mechanism unclear. Methods Low-dose (0.1ug) diphtheria toxin was given on GD11 to female C57-Bl6 FoxP3-DTR under a syngeneic pregnancy. On day 17, pup weight and gender was determined and UPI were removed and subject to FACS and confocal immunofluorescence. Results Subtle Treg depletion during pregnancy resulted in effector T cell influx preferentially to UPIs of antigenic (male) fetuses resulting in a reduction of fetal weights. Surprisingly, we also observed an increase of Treg numbers in the antigenic UPIs. Preliminary results indicate a local interaction between antigen-presenting cells, T cells and Treg in the previously depleted UPI. Conclusions Systemic interruption of Treg tolerance during pregnancy allows for maternal attack on antigenic fetuses. In the unperturbed UPI, the absence of Treg suggests that maternal tolerance is mediated elsewhere. In disrupted maternal tolerance, the repopulation of Treg to the UPI provides insight into Treg cellular interactions that may contribute to the re-establishment of tolerance under physiologic conditions.