Prevention of CpG-induced pregnancy disruption by adoptive transfer of in vitro-induced regulatory T cells

Objective: To elucidate the mechanism by which embryo-resorption and preterm birth were enhanced by pathogenic CpG motif and to develop a counter strategy for normal pregnancy outcome. Methods: This is an animal model-based study. In pregnant nonobese diabetic (NOD) mice and wild-type (WT) mice in the same strain background, an infection was mimicked by toll-like receptor 9 (TLR9) activation through CpG1826-injection. In vivo inactivation of IL-10 was performed to enhance pregnancy loss. Regulatory T cells induced by FTY720 in vitro from splenic CD4⁺CD25^-Foxp3^- cells (iTreg cells) were transferred to improve pregnancy outcomes in NOD mice. Results: Embryo-resorption and preterm birth were readily induced by CpG1826 in NOD mice, but not in WT mice. However, inactivation of IL-10 using neutralizing antibody injections enhanced pregnancy loss in WT mice exposed to CpG, while adoptive transfer of iTreg cells increased decidual Foxp3⁺ Treg cells and IL-10⁺ cell number and rescued pregnancy. Conclusions: NOD mice are prone to abortion and preterm birth. This can be attributed to lacking Treg cells and insufficient IL-10 expression. Adoptive transfer of iTreg cells can rescue CpG-mediated pregnancy failure.