During pregnancy, treg cells induce a privileged tolerant microenvironment at the fetal-maternal interface by up-regulating HO-1, TGF-β and LIF expression



The mechanisms underlying immune tolerance during pregnancy are poorly understood. We recently proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus, since we observed diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. We transferred mice undergoing abortion with Treg from mice having normal pregnancies, including normal pregnant and abortion-prone mice as controls. We evaluated decidual lymphocytes for their cytokine profile. The mRNA levels for several tolerance-associated cytokines were also analyzed. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Locally, augmented foxp3 levels could be observed. Surprisingly, after therapy the decidual levels of the Th1 cytokines IFN-γ and TNF-α were not diminished. The transfer of Treg dramatically up-regulated the expression of LIF, TGF-β and HO-1 at the fetal-maternal interface. Our data suggest that Treg-treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.