Regulation of T cell immunity within the female reproductive tract

描述（申请人提供）：女性生殖器粘膜是HIV感染的主要途径。这一建议将解决关于女性生殖道内T细胞免疫生物学知识的重大空白。基本问题，包括记忆CD8和CD4 T细胞分化、维持、运输、功能和保护贡献将在高通量可处理的小鼠模型中解决。记忆T细胞分化状态和功能的体外分析将辅以静态和活体成像，以获得T细胞免疫生物学和APC/抗原在这个复杂器官系统内运输的更完整的解剖图像。最近发现的局部记忆T细胞功能的机制，包括增强外周T细胞快速募集和激活局部先天免疫系统的能力，将被定义。记忆T细胞的循环模式通过不同的隔间的女性生殖道将定义异种共生。将评估局部和外周记忆T细胞群对生殖器病毒再次攻击的保护作用。这些研究将通过提供对该部位细胞免疫的调节、功能和保护机制的新见解，为开发在女性生殖道内暴露后迅速拦截艾滋病毒的T细胞疫苗提供信息。

DESCRIPTION (provided by applicant): The female genital mucosa is a major route of infection for HIV. This proposal will address significant gaps in knowledge regarding T cell immunobiology within the female reproductive tract. Fundamental issues, including memory CD8 and CD4 T cell differentiation, maintenance, trafficking, function, and contribution to protection will be addressed in a high-throughput tractable mouse model. Ex vivo analyses of memory T cell differentiation state, and function will be complemented by static and intravital imaging to yield a more complete anatomic picture of T cell immunobiology and APC/antigen trafficking within this complex organ system. Mechanisms underlying recently discovered functions of local memory T cells, including the ability to potentiate rapid peripheral T cell recruitment and activate the local innate immune system, will be defined. Memory T cell recirculation patterns through various compartments of the female reproductive tract will be defined by parabiosis. Contributions of local and peripheral memory T cell populations to protection against genital viral re-challenge will be assessed. These investigations will inform the development of T cell vaccines that rapidly intercept HIV upon exposure within the female reproductive tract by providing new insight into the regulation, function and protective mechanisms of cellular immunity at this site.