Regulation of T cell immunity within the female reproductive tract

描述（由申请人提供）：女性生殖器粘膜是HIV感染的主要途径。该提案将解决女性生殖道内T细胞免疫生物学知识方面的重大差距。基本问题，包括记忆CD 8和CD 4 T细胞的分化，维持，贩运，功能和保护的贡献将在高通量易处理的小鼠模型中得到解决。记忆T细胞分化状态和功能的离体分析将通过静态和活体成像来补充，以产生这个复杂器官系统内T细胞免疫生物学和APC/抗原运输的更完整的解剖图。最近发现的局部记忆性T细胞的功能，包括增强快速外周T细胞募集和激活局部先天免疫系统的能力，将被定义的机制。通过雌性生殖道的各个隔室的记忆T细胞再循环模式将由联体共生定义。将评估局部和外周记忆T细胞群对生殖器病毒再攻击的保护作用。这些研究将为T细胞疫苗的开发提供信息，这些疫苗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，在女性生殖道内暴露后快速拦截HIV。

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.