Cellular Immunity to Chlamydua at the Epithelial Interface

上皮界面对衣原体的细胞免疫

基本信息

批准号：
7883271
负责人：
RAYMOND Morris JOHNSON
金额：
$ 35.23万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7883271
关键词：
Address Animal Model Animals Antibiotics Antigen Presentation Pathway Antigen-Presenting Cells Antigens Bacterial Sexually Transmitted Diseases CD4 Positive T Lymphocytes Case Study Cell Communication Cell Line Cellular Immunity Cellular Immunology Centers for Disease Control and Prevention (U.S.)Chlamydia Chlamydia muridarum Chlamydia trachomatis Cicatrix Data Dendritic Cells Development Diagnosis Disease Ectopic Pregnancy Enrollment Epithelial Epithelial Cells Epithelium Future Genital system Goals Grant Host Defense Human Immune Immunity Immunohistochemistry Incidence Infection Infertility Investigation Light MHC Class I Genes MHC Class II Genes Mammalian Oviducts Measures Mediating Mus Occupations Participant Pathway interactions Phenotype Play Prevalence Public Health Reagent Reproductive Tract Infections Research Personnel Resolution Role Surface Surrogate Markers T cell response T-Lymphocyte T-Lymphocyte Subsets United States Vaccines Woman Work base cell type chronic pain design lymph nodes mouse model novel older women programs prophylactic reproductive therapeutic vaccine tissue tropism trafficking vaccine candidate vaccine development

项目摘要

DESCRIPTION (provided by applicant): Chlamydia trachomatis has a marked tissue tropism, replicating almost exclusively in epithelial cells lining the reproductive tract. The Chlamydia muridarum mouse model for human C. trachomatis disease has clearly demonstrated that T cells mediate protective immunity against reproductive tract infection. The central hypothesis of the grant is that Chlamydia-specific T cells responsible for sterilizing immunity interact with infected reproductive tract epithelial cells. Surprising little is known about T cell interactions with Chlamydia-infected epithelial cells. The major goal of the project is to understand which Chlamydia-specific T cell subsets eliminate infected epithelial cells from the reproductive tract, and how they accomplish that desired endpoint. Specifically the grant proposes to 1) To identify T cell subsets that interact with Chlamydia-infected oviduct epithelial cells to mediate sterilizing immunity, and identify the effector mechanism employed, 2) To define the specific antigen presentation pathways utilized by epithelial cells to present the Chlamydia antigens, 3) To determine the costimulatory and coinhibitory contributions of infected epithelial cells to activation of protective Chlamydia-specific T cells. To address these specific aims, unique oviduct epithelial cell lines have been generated to serve as antigen presenting cells for isolating Chlamydia- specific T cell lines. Understanding how T cells interact with infected epithelial cells to mediate sterilizing immunity may contribute to vaccine development by identifying surrogate markers for protective immunity that can be exploited in future vaccine trials. Chlamydia trachomatis infections of the reproductive tract have been the most commonly diagnosed bacterial STD in the United States since the early 1990's. In women, C. trachomatis infections commonly ascend into the Fallopian tubes causing infertility and ectopic pregnancies. Standard public health measures have not significantly decreased the incidence of C. trachomatis infections, therefore development of a Chlamydia vaccine would be a major step forward in public health. This grant proposes to contribute toward rational development of a Chlamydia vaccine by investigating how protective immunity works in the reproductive tract. Defining what protective T cells look like, and how they function, will be critical for designing and assessing future Chlamydia candidate vaccines.

描述（由申请人提供）：沙眼衣原体具有明显的组织质量，几乎完全在生殖道的上皮细胞中复制。人梭状芽孢杆菌疾病的穆里达鲁姆小鼠模型清楚地表明，T细胞介导保护性免疫抵抗生殖道感染。授予的中心假设是，负责消毒免疫力的衣原体特异性T细胞与感染的生殖道上皮细胞相互作用。关于与衣原体感染的上皮细胞的T细胞相互作用知之甚少。该项目的主要目的是了解哪些衣原体特异性T细胞亚群从生殖道中消除了受感染的上皮细胞，以及它们如何完成所需的终点。特别是向赠款提出的授予1）确定与感染的藻类的输卵管上皮细胞相互作用的T细胞子集，以介导无菌的免疫力，并确定所采用的效应机制，2）定义由上皮细胞使用的特定抗原呈递途径，以确定上皮细胞以促进chlamydia抗原，3）抗原抗原，3）保护性衣原体特异性T细胞。为了解决这些特定目的，已经生成独特的卵形上皮细胞系作为抗原呈递细胞，用于分离衣原体特异性T细胞系。了解T细胞如何与受感染的上皮细胞相互作用以介导灭菌免疫力可能会通过鉴定替代标志物的保护性免疫力来促进疫苗的发育，以在将来的疫苗试验中利用，这可以利用。自1990年代初期以来，生殖道的衣原体沙眼感染一直是美国最常见的细菌性病。在女性中，沙眼梭状芽孢杆菌感染通常会升入导致不育症和异位妊娠的输卵管。标准的公共卫生措施并未显着降低沙眼炎感染的发病率，因此，沙质疫苗的开发将是公共卫生方面的重要一步。该赠款建议通过研究保护性免疫在生殖道中的作用，从而为衣原体疫苗的合理发展做出贡献。定义保护性T细胞的外观以及它们的功能，对于设计和评估未来的衣原体候选疫苗至关重要。