Mechanisms of memory CD4 T cell-mediated immune protection against Chlamydia

项目总结/摘要 沙眼衣原体生殖器感染是美国最常报告的传染病 没有可用的疫苗。合理设计衣原体疫苗需要更好地了解 女性生殖道（FRT）粘膜内的保护性免疫机制。虽然它广泛 接受CD 4 T细胞在保护性免疫中对衣原体FRT感染起主要作用， CD 4 T细胞介导的免疫保护的潜在机制仍然知之甚少。这 应用程序提出了发展的分化，解剖分布和 保护性记忆CD 4 T细胞的维持以及它们如何被刺激以赋予保护性免疫 抵抗衣原体感染我们最近产生了几个衣原体特异性MHC II类四聚体， 衣原体FRT后内源性抗原特异性CD 4 T细胞的首次直接可视化 感染使用这些独特的工具，我们特别建议（i）检查保护性抗原特异性 记忆性CD 4 T细胞应答，导致衣原体从FRT中快速清除，和（ii）鉴定主要的 在FRT中刺激快速保护性记忆CD 4 T细胞应答的抗原呈递细胞。我们 预计识别记忆性CD 4 T细胞对衣原体再感染的保护作用， 阐明免疫记忆是如何在宿主体内维持和重新激活的， 未来急需的衣原体疫苗的设计。

PROJECT SUMMARY/ABSTRACT Chlamydia trachomatis genital infection is the most commonly reported infectious disease in the United States with no vaccine available. The rational design of a chlamydia vaccine requires improved understanding of the protective immune mechanisms within the female reproductive tract (FRT) mucosa. Although it is broadly accepted that CD4 T cells play a predominant role in protective immunity against Chlamydia FRT infection, the mechanisms underlying CD4 T cell-mediated immune protection remain to be poorly understood. This application proposes to develop a thorough understanding of the differentiation, anatomical distribution and maintenance of protective memory CD4 T cells and how they are stimulated to confer protective immunity against Chlamydia. We recently generated several Chlamydia-specific MHC Class II tetramers, which allow for the first time direct visualization of endogenous, antigen-specific CD4 T cells following Chlamydia FRT infection. Using these unique tools, we specifically propose to (i) examine the protective antigen-specific memory CD4 T cell responses that lead to fast Chlamydia clearance from the FRT, and (ii) identify the major antigen-presenting cells that stimulate the rapid protective memory CD4 T cell response in the FRT. We anticipate that identifying the protective aspects of memory CD4 T cell responses to Chlamydia reinfection and elucidating how immunological memory is maintained and reactivated in the host will provide important insights into the future design of an urgently needed chlamydia vaccine.