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

• Main Authors: Yi Lin, Xiaorui Liu, Bin Shan, Ji Wu, Surendra Sharma, Yun Sun
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3979847?pdf=render

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.