Uterine NK Cells in Primate Pregnancy

灵长类动物妊娠中的子宫 NK 细胞

• 批准号: 7926996
• 负责人: THADDEUS G GOLOS
• 金额: $ 59.13万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7926996
• 关键词: Abbreviations; Address; Animal Model; Animals; Biological; Blood Vessels; CD209 gene; Cells; Chorionic Gonadotropin; Clinical; Cytotoxic T-Lymphocytes; Data; Decidua; Dendritic Cells; Development; Developmental Delay Disorders; Elements; Endometrial; Endometrium; Endothelial Cells; Epithelial; Fetal Growth; Funding; Growth; HLA G antigen; Health; Histocompatibility Antigens Class I; Homologous Gene; Human; Immune; Immune response; Immunoglobulins; In Vitro; Infertility; Leukocyte Trafficking; Leukocytes; MHC Class I Genes; MHC Interaction; Macaca mulatta; Modeling; Modification; Molecular Analysis; Monkeys; Monoclonal Antibodies; Morphogenesis; Natural Killer Cells; Neonatal; Passive Immunization; Personal Satisfaction; Phenotype; Physiological; Placenta; Placental Lactogen; Population; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Primates; Public Health; Research; Role; Sampling; Signal Transduction; Smooth Muscle Actin Staining Method; Spiral Artery of the Endometrium; Spontaneous abortion; Staging; Surface; Syncytiotrophoblast; System; T-Lymphocyte; Testing; Therapeutic; Transcript; Vascularization; Villous; abstracting; angiogenesis; base; cancer immunotherapy; cytotrophoblast; implantation; in vivo; killer inhibitory receptor; macrophage; nonhuman primate; novel; preclinical study; pregnancy disorder; pregnant; receptor; research study; response; success; therapy development; trophoblast; vasculogenesis; von Willebrand Factor

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:

摘要 对胎盘MHC-I类分子表达的免疫反应被认为是重要的，但无论是 这种反应在人类或非人类灵长类动物身上的机制和意义还没有被很好地理解。我们 最近有研究表明，在怀孕的恒河猴中被动免疫MAMU-AG，即恒河猴 非经典滋养层细胞MHC I类分子被认为是人类白细胞抗原G的同源物，有广泛的 胎盘绒毛生长和血管形成的发育延迟，改变 母体蜕膜血管通过侵袭性绒毛外滋养细胞和改变蜕膜白细胞对 植入。假设母体NK细胞在识别胎盘MHC中起关键作用，我们现在 有试点数据表明NK细胞免疫衰竭对妊娠结局有负面影响， 在抗CD16或抗CD8治疗后一周内导致自然流产。我们建议这是 胎盘MHC-I类分子在母体免疫应答中发挥重要作用的证据 在灵长类动物中怀孕，并将进一步研究这些反应的机制和意义 具体目标：

项目成果

Identification and characterization of a novel luciferase-like protein in the human female reproductive tract.

人类女性生殖道中新型荧光素酶样蛋白的鉴定和表征。

• DOI: 10.1210/jc.2004-0022
• 发表时间: 2004
• 期刊: The Journal of clinical endocrinology and metabolism.
• 作者: Khorram,O;Garthwaite,M;Johnson,MS;Denessiouk,KA;Han,G;Guo,T;McPhaul,LW;Magee,TR;Westerman,B;Golos,TG
• 通讯作者: Golos,TG