Uterine NK Cells in Primate Pregnancy

灵长类动物妊娠中的子宫 NK 细胞

• 批准号: 7577786
• 负责人: THADDEUS G GOLOS
• 金额: $ 57.41万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7577786
• 关键词: Address; Antibodies; Biological; Cells; Data; Decidua; Development; Developmental Delay Disorders; Endometrial; Endometrium; Growth; HLA G antigen; Histocompatibility Antigens Class I; Homologous Gene; Human; Immune; Immune response; Infertility; Leukocytes; MHC Class I Genes; Macaca mulatta; Modeling; Modification; Natural Killer Cells; Peripheral; Placenta; Population; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Primates; Public Health; Role; Site; Spontaneous abortion; Therapeutic; Vascularization; Villous; abstracting; cancer immunotherapy; implantation; nonhuman primate; preclinical study; pregnancy disorder; pregnant; response; success; therapy development; trophoblast

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:

抽象的 对胎盘 MHC I 类表达的免疫反应被认为很重要，但 这种反应在人类或非人类灵长类动物中的机制和意义尚不清楚。我们 最近表明，在对 Mamu-AG 进行被动免疫的怀孕恒河猴中，恒河猴 非经典滋养层 MHC I 类分子被认为是 HLA-G 的同源物，有广泛的应用 胎盘绒毛生长和血管化的发育迟缓，修饰的破坏 侵入性绒毛外滋养层母体蜕膜血管，并改变蜕膜白细胞对 植入。假设母体 NK 细胞对于识别胎盘 MHC 至关重要，我们现在 有试验数据表明 NK 细胞免疫耗竭对妊娠结局有负面影响， 抗CD16或抗CD8治疗后一周内引起自然流产。我们建议这是 胎盘 MHC I 类分子在母体免疫反应中发挥重要作用的证据 灵长类动物怀孕，并将进一步研究两种反应的机制和意义 具体目标：