Generation of a TCR transgenic mouse to study Chlamydia genital tract infection

 描述（由申请人提供）：衣原体感染是美国性传播疾病的主要原因。如果一个有效的疫苗是成为现实，迫切需要更多的了解粘膜表面的保护性免疫衣原体。本申请提出开发TCR转基因小鼠以揭示衣原体感染生殖道期间粘膜CD4 T细胞生物学的基本方面。我们的实验方法是独特的，因为它将利用自然的感染途径，一个建立的小鼠感染模型，其中CD4 T细胞参与病原体清除，并涉及使用我们将开发的试剂和技术直接可视化病原体特异性CD4 T细胞。我们的申请特别提出，（i）鉴定在生殖道中驱动CD4 T效应细胞引发的抗原呈递细胞亚群，和（ii）定义上生殖道中保护性免疫所需的T CD4 T细胞记忆库的异质性。了解这两个问题将是至关重要的，以产生一种疫苗，对衣原体，最重要的病原体之一，影响生殖健康的年轻妇女在美国。

 DESCRIPTION (provided by applicant): Chlamydia infections are a major cause of sexually transmitted disease in the US. Greater understanding of protective immunity to Chlamydia at mucosal surfaces is urgently required if an effective vaccine is to become a reality. This application proposes to develop a TCR transgenic mouse to uncover fundamental aspects of mucosal CD4 T cell biology during infection of the reproductive tract with Chlamydia. Our experimental approach is unique in that it will utilize a natural route of infection, an establishe mouse model of infection where CD4 T cells participate in pathogen clearance, and involve direct visualization of pathogen-specific CD4 T cells using reagents and techniques that we will develop. Our application specifically proposes to, (i) identify antigen presenting cell subsets tha drive CD4 T effector cell priming in the reproductive tract, and (ii) define the heterogeneity of te CD4 T cell memory pool required for protective immunity in the upper reproductive tract. Understanding both these issues will be vitally important for the generation of a vaccine against Chlamydia, one of the most important pathogens affecting the reproductive health of young women in the US.