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

项目摘要/摘要 沙眼衣原体生殖道感染是美国最常见的传染病 在没有疫苗的情况下。衣原体疫苗的合理设计需要更好地理解 女性生殖道(FRT)粘膜内的保护性免疫机制。尽管它被广泛地 认识到CD4T细胞在预防衣原体FRT感染的保护性免疫中起主要作用， CD4T细胞介导的免疫保护机制尚不清楚。这 应用程序建议发展对分化，解剖分布和 保护性记忆CD4T细胞的维持及其如何被刺激以赋予保护性免疫 对抗衣原体。我们最近产生了几个衣原体特异的MHC II类四聚体，它们允许 衣原体FRT后首次直接显示内源性、抗原特异性的CD4T细胞 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CD4T细胞反应导致衣原体快速从FRT中清除，以及(Ii)识别主要 抗原提呈细胞在FRT中刺激快速保护性记忆的CD4T细胞反应。我们 预计识别记忆中CD4T细胞对衣原体再感染的保护性反应 阐明免疫记忆是如何在宿主中维持和重新激活的将提供重要的见解 关于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.