Regulation of T cell immunity within the female reproductive tract

女性生殖道内 T 细胞免疫的调节

• 批准号: 8703487
• 负责人: DAVID MASOPUST
• 金额: $ 47.52万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703487
• 关键词: Acute; Address; Anatomy; Antigens; Biological Models; CD4 Positive T Lymphocytes; CD8B1 gene; Cell Mobility; Cell physiology; Cells; Cellular Immunity; Chronic; Complement; Complex; Coupled; Environment; Epithelium; Experimental Genetics; Female; Genital system; Goals; HIV; HIV Infections; Image; Immune response; Immune system; Immunity; Immunobiology; Infection; Intercept; Investigation; Knowledge; Longevity; Lymphocyte; Lymphoid; Maintenance; Memory; Modeling; Mucous Membrane; Mus; Natural Killer Cells; Parabiosis; Pattern; Peripheral; Population; Publishing; Regulation; Role; Route; Sampling; Site; T cell differentiation; T cell regulation; T cell response; T memory cell; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Vaccines; Viral; base; body system; cytokine; design; insight; intravital imaging; intravital microscopy; migration; mouse model; novel; pathogen; public health relevance; reproductive; residence; response; sensor; trafficking; two-photon; vaccine development

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.

描述(申请人提供)：女性生殖器粘膜是感染艾滋病毒的主要途径。这项建议将解决有关女性生殖道内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CD4T细胞的分化、维持、贩运、功能和对保护的贡献，将在一个高通量、易驯化的小鼠模型中解决。对记忆T细胞分化状态和功能的体外分析将得到静态和活体成像的补充，以得出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细胞功能的潜在机制，包括增强快速外周T细胞招募和激活局部先天免疫系统的能力，将被定义。通过女性生殖道不同间隔的记忆T细胞再循环模式将被定义为异种共生。将评估局部和外周记忆T细胞群体对预防生殖器病毒再次挑战的贡献。这些研究将为T细胞疫苗的开发提供信息，这种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时迅速拦截艾滋病毒。