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Cervical T Cell Immunity to C. trachomatis

宫颈 T 细胞对沙眼衣原体的免疫

基本信息

批准号：
7979772
负责人：
ALISON J. QUAYLE
金额：
$ 14.3万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7979772
关键词：
Address Animal Model Antibiotic Therapy Antigen Presentation Antigen Presentation Pathway Antigen-Presenting Cells Antigens Area Bacterial Infections Blood Circulation CD3 Antigens CD8B1 gene Cell secretion Cells Cervical Cervix Uteri Characteristics Chlamydia Chlamydia trachomatis Chronic Chronic Disease Clone Cells Contracts Cross Presentation Cytoplasmic Granules Data Development Diagnostic Disease Endocervical Mucosa Endocervix Epithelial Epithelial Cells Epithelium Event Foundations Frequencies HIV Infections HIV-1 Health Care Costs Histocompatibility Antigens Class II Homing Host resistance Human Immune Immune response Immune system Immunity Immunology Infection Infection Control Knowledge Laboratories Local Microbicides Louisiana Lymphocyte Function Lymphoid Lytic Maintenance Mediating Methodology Modeling Molecular Profiling Mus Organism Outcome Pathway interactions Pattern Phase Phenotype Play Population Predisposition Process Production Research Research Design Research Infrastructure Resources Role Sampling Site Source Specimen Structure of thyroid parafollicular cell T-Lymphocyte Testing Time Study Tissues Vaccines Vacuole Woman cohort cytokine design human disease in vivo killings mucosal site pathogen patient population peripheral blood reproductive response trafficking vaccination strategy

项目摘要

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection. Devastating reproductive consequences of chronic C. trachomatis disease and a predisposition to HIV infection make progress towards the development of effective vaccination strategies imperative. However, limited information in several key areas has severely hampered progress in this area. Animal models have shown that T cell responses are central to host resistance but do not reproduce all the critical features of human disease. C. trachomatis is an obligate intracellular pathogen that primarily infects columnar epithelial cells of the endocervix in women, yet little is known either of the inductive or effector phases of local immunity in these tissues. Immune cells at mucosal sites are phenotypically and functionally distinct from their counterparts in the circulation and it is increasingly clear that the local milieu plays an important role in regulating local immunity. Nevertheless, almost all human studies to date have focused, perhaps inappropriately, on C. trachomatis-specific immunity in the circulation, since great difficulties have, to date, attended isolation of endocervical lymphoid ceils. Here, each of these issues will be addressed. The primary focus of this application is to characterize T cell immune responses at the primary site of C. trachomatis infection in the human endocervix with the underlying hypothesis that activity of these subpopulations, rather than circulating T cells, most accurately reflects the critical host response against this pathogen. Initially, the local immune milieu will be characterized using secretions and cytobrush cell specimens from C. trachomatis-infected women both pre-and post-antibiotic treatment and from uninfected controls. Comparisons with circulating T cell populations will clarify unique features of the mucosal T cell repertoire. Next, the frequencies, cytokine expression profiles and lytic activities of endocervical and circulating C. trachomatis-specific CD4 and CD8 T cells both will be more closely defined both directly ex vivo and in cloned cell populations. Finally, in studies with our T cell clones, processing and presentation of C. trachomatis antigens will be characterized, using immortalized endocervical columnar epithelial cells that are genetically or biochemically manipulated for directed inhibition of specific intraceUular trafficking pathways. This study design will clarify interactions between C. trachomatis and the cervical immune system that will ultimately aid greatly in delineating protective immune responses against C. trachomatis and the development of effective vaccines.

沙眼衣原体是最普遍的性传播细菌感染。毁灭性的生殖