Phenotypic and functional characterization of primary human lymphoid dendritic cells, with a focus on XCR1+ DC

树突状细胞（DC）是免疫系统中的细胞，其“专业地”摄取蛋白质抗原并将其呈递给T细胞。随后T细胞和DC之间的“对话”对于决定对抗原的“免疫”和“耐受”至关重要。虽然在小鼠中DC亚群功能的理解方面取得了重要进展，但关于原代人常规DC的信息仍然令人惊讶地稀少，显然是因为它们在血液和淋巴组织中的数量非常低并且缺乏标记物。相反，几乎所有的人体实验都是用体外单核细胞产生的DC进行的，这些细胞仅不完全反映原代DC。最近，我们鉴定了一种亚群特异性DC表面分子（XCR1受体），其他人定义了DC上的其他分子。这些进展，加上改进的细胞分离技术，现在可以更好地表征原代人DC。在该项目中，我们打算完善目前对原代人血DC向T细胞进行抗原（交叉）呈递的初步认识，并确定淋巴组织和外周器官中人类DC的基本表型和免疫功能。这些信息将显示在小鼠中开发的概念是否也适用于健康和（自身免疫）疾病中的人类DC。所获得的知识是我们和其他人未来开发新型疫苗的先决条件，其中通过将抗原直接靶向体内XCR1+ DC来实现对肿瘤和细胞内病原体的细胞毒性免疫。

Dendritic cells (DC) are cells in the immune system, which “professionally” take up protein antigens and present it to T cells. The ensuing “dialogue” between T cells and DC is pivotal for the decision between “immunity” and “tolerance” to an antigen. While important advances have been made in the understanding of DC subset function in the mouse, information on primary human conventional DC remained surprisingly scarce, apparently because of their very low numbers in blood and lymphoid tissues and the lack of markers. Instead, almost all experiments in the human have been performed with DC generated from monocytes in vitro, cells which only incompletely reflect primary DC. Very recently, we characterized a subset-specific DC surface molecule (XCR1 receptor), additional molecules on DC were defined by others. These advances, together with improved cell isolation techniques, allow now to better characterize primary human DC. In the project, we intend to refine the current initial understanding of primary human blood DC for antigen (cross-) presentation to T cells and to define the basic phenotype and immune function of human DC resident in lymphoid tissues and peripheral organs. This information will show whether the concepts developed in the mouse also hold true for human DC in health and (autoimmune) disease. The gained knowledge is a prerequisite for the future development of novel vaccines by us and others, in which cytotoxic immunity to tumors and intracellular pathogens is to be achieved by direct targeting of antigen to XCR1+ DC in vivo.