Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

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Abstract
The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing 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. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN‐γ and TNF‐α were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF‐β and heme oxygenase‐1 at the fetal‐maternal interface were dramatically up‐regulated after Treg transfer, while the levels of indolamine 2,3‐dioxygenase remained unchanged. 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.