DECIDUAL T LYMPHOCYTE PHENOTYPE AND FUNCTION

蜕膜 T 淋巴细胞表型和功能

• 批准号: 2207633
• 负责人: KENT D HEYBORNE
• 金额: $ 9.29万
• 依托单位: HEALTHONE ALLIANCE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2000-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2207633
• 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

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.

有大量证据支持母胎免疫的作用， 在介导各种各样的生殖并发症中的相互作用， 包括不孕症、复发性流产、先兆子痫、子宫内 生长迟缓和早产。这些问题需要大量的 孕产妇和新生儿发病率和死亡率。建议的研究 本文旨在增强对母-胎妊娠的理解， 免疫关系，重点是描述表型和 小鼠模型中蜕膜T淋巴细胞的功能。间接 T细胞参与妊娠的证据来自于大量的研究 详细描述了T细胞亚群和总体T细胞群在 怀孕T细胞参与妊娠的更直接证据是 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，因为进一步的研究取决于这一知识。 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 从几种生殖组织中获得的淋巴细胞的产生 提出了妊娠期的注意事项。第二个具体目标提出， 通过以下方式探测蜕膜T细胞的特定亚群的功能： 通过mAb注射选择性耗竭T细胞亚群。因为证据 存在涉及异常免疫激活介导的各种 生殖并发症，第三个目标研究了 不同T细胞亚群的选择性免疫激活在 怀孕 初步实验表明， 滋养层细胞由γ δ细胞亚群组成，这是唯一的 滋养层细胞的直接免疫识别。因此，这 γ δ细胞亚群是在那些被选择用于激活的细胞中。 激活将通过刺激剂量的注射mAb，或通过 注射刺激肽。初步研究表明， 某些此类操作的影响，特别是消耗 α β T细胞在围着床期，所以具体 第四个目的是研究这种情况下妊娠丢失的机制， 妊娠衰竭。这将通过综合办法来实现 利用免疫组织化学研究， 妊娠丢失，通过双耗竭实验，其中可能的效应子 亚群用α β T细胞耗竭和细胞因子编码 再吸收妊娠的胎盘外植体的上清液分析。