Uterine NK Cells in Primate Pregnancy

灵长类动物妊娠中的子宫 NK 细胞

基本信息

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
项目类别：
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

项目摘要

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。我们最近的研究表明，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：

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.
影响因子：
0
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