Characterization of Tau Lymphocyte Modulation in Pregnancy

妊娠期 Tau 淋巴细胞调节的特征

• 批准号: 7707953
• 负责人: Leela E Noronha
• 金额: $ 7.28万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-16 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707953
• 关键词: Alloantigen; Allogenic; Allografting; Antibodies; Antigens; Biological Assay; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cancer Biology; Cell Separation; Cells; Cellular Immunity; Communicable Diseases; Contraceptive methods; Cytolysis; Cytotoxic T-Lymphocytes; Defect; Disease; Enzymes; Equus caballus; Excision; Exhibits; Fetus; Flow Cytometry; Generations; Genetic; Goals; Human; IL2RA gene; Immune response; Immune system; Immunity; Impairment; In Vitro; Infertility; Lead; Link; Lymphocyte; Lymphocyte Subset; Mammals; Methods; Minor Histocompatibility Antigens; Modeling; Mothers; Organism; Peripheral; Polymerase Chain Reaction; Population; Pregnancy; Pregnancy loss; Prevention; Process; Production; Proliferating; RNA-Directed DNA Polymerase; Research; Sorting - Cell Movement; T-Cell Immunologic Specificity; T-Lymphocyte; Techniques; Testing; Time; Transplantation; Transplantation Immunology; base; cell mediated immune response; cytokine; design; fetal; insight; killings; neoplastic cell; pregnant; research study; success; tau Proteins

DESCRIPTION (provided by applicant): The success of mammalian pregnancy is inherently dependent upon maternal immunological tolerance of the genetically foreign fetus. Understanding the mechanism of this tolerance can contribute to the prevention of early pregnancy loss and pre-natal disease, and suggest new methods for contraception. This project is designed to contribute to the long-term goal of elucidating the immunological mechanisms of maternal-fetal tolerance. It focuses on the peripheral modulation of cell-mediated immunity that has been observed during pregnancy in the horse and other species. The hypothesis to be tested is that pregnancy induces systemic tolerance in the CD4+ T cell population of the pregnant mare in a manner that is not specific for paternal alloantigen. By establishing pregnancies of differing genetic compatibilities and examining the maternal immune response, this project will investigate the following specific aims: 1. To determine the antigen specificity of the T cell impairment observed during the pregnant state. 2. To determine the respective contributions of the CD4+ and CD8+ lymphocyte subsets to the defect in cytotoxic T lymphocyte activity. Techniques to be utilized in this project include: flow cytometry, enzyme-linked immunosorbant assays (ELISA), reverse-transcriptase real-time polymerase chain reaction, cell sorting, and cytotoxic T lymphocyte (CTL) killing assays. This project takes advantage of the naturally occurring modulation of maternal immunity in equine pregnancy that offers unique insights into the fetal-maternal immunological relationship in mammals. This research will help advance the understanding of why a fetus is accepted by the mother's immune system. It will provide valuable information that will contribute to the fields of infertility and contraception. Furthermore, the immunological concepts surrounding this process are also relevant to the fields of transplantation biology, cancer, and infectious diseases.

描述（由申请人提供）：哺乳动物妊娠的成功本质上取决于遗传外胎胎儿的母体免疫学耐受性。了解这种耐受性的机制可以有助于预防早期妊娠丧失和产后疾病，并提出新的避孕方法。该项目旨在为阐明母亲耐受性的免疫机制的长期目标做出贡献。它着重于在马和其他物种怀孕期间观察到的细胞介导的免疫的外围调节。要检验的假设是，怀孕诱导了怀孕母马的CD4+ T细胞群体的全身耐受性，这种方式对父亲同种剂而言并非特定。通过建立不同遗传兼容性的怀孕并检查母体免疫反应，该项目将研究以下特定目的：1。确定在怀孕状态期间观察到的T细胞损伤的抗原特异性。 2。确定CD4+和CD8+淋巴细胞亚群对细胞毒性T淋巴细胞活性缺陷的各自贡献。该项目中要使用的技术包括：流式细胞仪，酶联免疫吸收测定法（ELISA），反向转录酶实时聚合酶链反应，细胞分配和细胞毒性T淋巴细胞（CTL）杀伤测定法。该项目利用了马妊娠中孕产妇免疫的自然调节，该调节为哺乳动物的胎儿母性免疫关系提供了独特的见解。 这项研究将有助于促进对为什么母亲免疫系统接受胎儿的理解。它将提供有价值的信息，这些信息将有助于不育和避孕的领域。此外，围绕此过程的免疫学概念也与移植生物学，癌症和传染病领域有关。