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DECIDUAL T LYMPHOCYTE PHENOTYPE AND FUNCTION

蜕膜 T 淋巴细胞表型和功能

基本信息

批准号：
2889257
负责人：
KENT D HEYBORNE
金额：
$ 9.64万
依托单位：
HEALTHONE ALLIANCE
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-30 至 2001-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2889257
关键词：
T lymphocyte biological models cell population study cell sorting complementary DNA decidua embryo implantation gestational age hybridomas immunocytochemistry laboratory mouse monoclonal antibody phenotype polymerase chain reaction pregnancy immunology spontaneous abortion trophoblast

项目摘要

Substantial evidence exists supporting a role for maternal-fetal immune interactions in mediating a wide variety of reproductive complications, including infertility, recurrent miscarriage, preeclampsia, intrauterine growth retardation, and preterm birth. These problems entail substantial maternal and neonatal morbidity and mortality. The studies proposed herein are intended to enhance the understanding of the maternal-fetal immune relationship by focusing on the description of both phenotype and function of decidual T lymphocytes in a murine model. Circumstantial evidence for T cell involvement in gestation comes from numerous studies detailing changes in T cell subsets and the overall T population during gestation. More direct evidence of T cell involvement in pregnancy is presented here in the form of preliminary data. The first specific aim involves extensive phenotypic characterization of the decidual T cell population, since further studies are predicated upon this knowledge. Detailed and definitive studies using flow cytometry, immunohistochemistry, quantitative cDNA analysis, and hybridoma production of lymphocytes obtained from reproductive tissues from several points during gestation are proposed. The second specific aim proposes to probe the function of specific subsets of decidual T cells by selective depletion of T cell subsets by mAb injection. Since evidence exists implicating abnormal immune activation in mediating a variety of reproductive complications, specific aim number three. investigates the effect of selective immune activation of various T cell subsets during gestation. Preliminary experiments demonstrate recognition of trophoblasts by a subset of gamma delta cells, and this is the only direct immune recognition of trophoblasts yet demonstrated. As such, this gamma delta cell subset is amongst those chosen for activation. Activation will be achieved by stimulatory doses of injected mAb, or by injection of stimulatory peptide. Preliminary studies indicate profound effects of certain of such manipulations, specifically the depletion of alpha beta T cells during the periimplantation period, and so specific aim number four investigates the mechanism of pregnancy loss in such depleted pregnancies. This will be accomplished by a combined approach using immunohistochemical studies of tissues of depleted mice undergoing pregnancy loss, by double depletion experiments wherein possible effector subsets are codepleted with alpha beta T cell depletions, and by cytokine analysis of supernatants of placental explants of resorbing pregnancies.

有大量证据支持母婴免疫的作用在调节各种生殖并发症方面的相互作用，包括不孕症、反复流产、先兆子痫、宫内发育迟缓和早产。这些问题带来了大量的孕产妇和新生儿发病率和死亡率。这项研究建议本文旨在提高对母婴关系的认识通过重点描述表型和免疫关系蜕膜T淋巴细胞在小鼠模型中的功能。间接证据 T细胞参与妊娠的证据来自大量研究详细描述了T细胞亚群和T细胞总数的变化怀孕了。T细胞参与怀孕的更直接证据是这里以初步数据的形式呈现。第一个具体目标涉及蜕膜T细胞的广泛表型特征人口，因为进一步的研究是以这一知识为基础的。使用流式细胞术进行详细和明确的研究，免疫组织化学、定量cdna分析和杂交瘤几种动物生殖组织中淋巴细胞的产生提出了孕期应注意的问题。第二个具体目标是提出目的：探讨蜕膜T细胞亚群的功能通过注射单抗选择性去除T细胞亚群。因为有证据存在与异常免疫激活有关的调节多种生殖并发症，具体目标三。调查不同T细胞亚群选择性免疫激活对机体免疫功能的影响怀孕了。初步实验表明，识别滋养层细胞的一部分，这是唯一的目前尚未证实滋养层细胞的直接免疫识别。因此，这是伽马三角洲细胞亚群是被选择激活的细胞之一。激活将通过注射刺激性剂量的单抗或通过注射刺激性多肽。初步研究表明，某些此类操纵的影响，特别是耗尽围植入期的α-βT细胞，如此特异目的四探讨妊娠丢失的发生机制。精疲力竭的怀孕。这将通过一种综合的方法来实现应用免疫组织化学方法对耗竭小鼠的组织进行妊娠丢失，通过双耗竭实验，其中可能的效应者亚群与α-βT细胞耗竭和细胞因子共同耗尽吸收妊娠胎盘外植体上清液分析。