Uterine NK Cells in Primate Pregnancy

摘要 对胎盘MHC I类表达的免疫应答被认为是重要的，然而， 这种反应在人类或非人灵长类动物中的机制和意义都很清楚。我们 最近表明，在对Mamu-AG被动免疫的怀孕恒河猴中， 非经典滋养层MHC I类分子被认为是HLA-G的同源物，存在广泛的 绒毛生长和胎盘血管化的发育延迟， 通过浸润性绒毛外滋养层细胞破坏母体蜕膜血管，并改变蜕膜白细胞对 置入假设母体NK细胞在识别胎盘MHC中起关键作用，我们现在 有初步数据表明NK细胞免疫耗竭对妊娠结局有负面影响， 在抗CD 16或抗CD 8治疗后一周内引起自然流产。我们认为，这是 胎盘MHC I类分子在母体免疫应答中的重要作用的证据， 怀孕的灵长类动物，并将进一步研究这些反应的机制和意义与两个 具体目标：

ABSTRACT The immunological response to placental MHC class I expression is considered to be important, yet neither the mechanisms nor the significance of this response in humans or nonhuman primates is well understood. We have recently shown that in pregnant rhesus monkeys passively immunized against Mamu-AG, the rhesus nonclassical trophoblast MHC class I molecule thought to be a homolog of HLA-G, there is a broad developmental delay in villous growth and vascularization of the placenta, a disruption of the modification of maternal decidual vessels by invasive extravillous trophoblasts, and altered decidual leukocyte responses to implantation. Hypothesizing that maternal NK cells are critical in the recognition of placental MHC, we now have pilot data demonstrating that NK cell immunodepletion has a negative impact on pregnancy outcome, causing spontaneous abortion within a week after anti-CD16 or anti-CD8 treatment. We propose that this is evidence for an important role of placental MHC class I molecules in the maternal immunological response to pregnancy in primates, and will further study the mechanisms and significance of these responses with two specific aims: