Köstlin Natascha, Hofstädter Kathrin, Ostermeir Anna-Lena, Spring Bärbel, Leiber Anja, Haen Susanne, Abele Harald, Bauer Peter, Pollheimer Jürgen, Hartl Dominik, Poets Christian F, Gille Christian
Department of Neonatology, University Children's Hospital Tuebingen, 72076 Tuebingen, Germany;
Department of Pathology, University Hospital Tuebingen, 72076 Tuebingen, Germany;
J Immunol. 2016 Feb 1;196(3):1132-45. doi: 10.4049/jimmunol.1500340. Epub 2015 Dec 28.
Tolerance induction toward the semiallogeneic fetus is crucial to enable a successful pregnancy; its failure is associated with abortion or preterm delivery. Skewing T cell differentiation toward a Th2-dominated phenotype seems to be pivotal in maternal immune adaption, yet underlying mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that mediate T cell suppression and are increased in cord blood of healthy newborns and in peripheral blood of pregnant women. In this study, we demonstrate that granulocytic MDSCs (GR-MDSCs) accumulate in human placenta of healthy pregnancies but are diminished in patients with spontaneous abortions. Placental GR-MDSCs effectively suppressed T cell responses by expression of arginase I and production of reactive oxygen species and were activated at the maternal-fetal interface through interaction with trophoblast cells. Furthermore, GR-MDSCs isolated from placenta polarized CD4(+) T cells toward a Th2 cytokine response. These results highlight a potential role of GR-MDSCs in inducing and maintaining maternal-fetal tolerance and suggest them as a promising target for therapeutic manipulation of pregnancy complications.
诱导对半同种异体胎儿的耐受性对于成功妊娠至关重要；耐受性诱导失败与流产或早产有关。使T细胞分化偏向以Th2为主导的表型似乎在母体免疫适应中起关键作用，但其潜在机制尚未完全了解。髓系来源的抑制细胞（MDSCs）是介导T细胞抑制的先天性免疫细胞，在健康新生儿的脐带血和孕妇的外周血中数量增加。在本研究中，我们证明粒细胞MDSCs（GR-MDSCs）在健康妊娠的人胎盘中积聚，但在自然流产患者中减少。胎盘GR-MDSCs通过精氨酸酶I的表达和活性氧的产生有效抑制T细胞反应，并通过与滋养层细胞相互作用在母胎界面被激活。此外，从胎盘中分离出的GR-MDSCs使CD4(+) T细胞向Th2细胞因子反应极化。这些结果突出了GR-MDSCs在诱导和维持母胎耐受性中的潜在作用，并表明它们是治疗妊娠并发症的一个有前景的靶点。
