Role of CD8+ dendritic cells in antigen (cross-) presentation and cytotoxic immunity of the mouse and the human

CD8 树突状细胞在小鼠和人类抗原（交叉）呈递和细胞毒性免疫中的作用

• 批准号: 173831869
• 负责人: Professor Dr. Richard Kroczek
• 金额: --
• 依托单位: Projektgruppe 1: Immunologische Abwehrmechanismen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/173831869?language=en
• 关键词: Role; CD8+; dendritic; cells; antigen

In the immune system, antigen is taken up and processed by “dendritic cells” (DC), of which an important subgroup (20%) are CD8+DC. The exact contribution of CD8+DC to antigen (cross-)presentation, an absolutely central process for the establishment of immune tolerance and generation of immunity, could not be assessed to date due to the lack of suitable experimental systems. Numerous data, however, point to a pivotal role of these CD8+DC in the development of a cytotoxic response to viruses, intracellular bacteria, and certain tumors. Based on the identification of a surface receptor, which is exclusively expressed in cross-presenting CD8+DC, we will be able to genetically delete these DC in mice and thus define their role in the immune system at steady state (tolerance) and in infection (immunity). These studies will be accompanied by numerous approaches aimed at defining the function of CD8+ DC in various organs of wild type mice. At the same time, we will identify the human counterpart of murine CD8+DC. These human DC will be phenotypically characterized and functionally tested, in particular for their capacity to (cross-)present antigen to CD8+ T cells, which are the mainstay of the cytotoxic immune defense. These basic studies will provide information which may enable us in the future to develop fundamentally new types of vaccines optimized for the induction of cytotoxic T cells directed against viral diseases and tumors.

在免疫系统中，抗原被“树突状细胞”（DC）摄取和加工，其中一个重要的亚群（20%）是CD8+DC。由于缺乏合适的实验系统，CD8+DC对抗原（交叉）呈递（建立免疫耐受和产生免疫力的绝对核心过程）的确切贡献迄今无法评估。然而，许多数据表明，这些CD8+DC在对病毒、细胞内细菌和某些肿瘤的细胞毒性反应的发展中起关键作用。基于表面受体的鉴定，其仅在交叉呈递的CD8+DC中表达，我们将能够在小鼠中遗传删除这些DC，从而确定它们在稳态（耐受性）和感染（免疫性）时在免疫系统中的作用。这些研究将伴随着许多旨在定义野生型小鼠各种器官中CD8+ DC功能的方法。同时，我们将鉴定鼠CD8+DC的人类对应物。将对这些人DC进行表型表征和功能测试，特别是测试它们将抗原（交叉）呈递给CD8+ T细胞的能力，这是细胞毒性免疫防御的支柱。这些基础研究将提供信息，使我们能够在未来开发出针对病毒性疾病和肿瘤诱导细胞毒性T细胞的新型疫苗。