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，它“专业”地吸收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”对于决定对某种抗原的“免疫”和“耐受”是至关重要的。虽然对小鼠树突状细胞亚群功能的了解已经取得了重要进展，但关于人类原代常规树突状细胞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少，而且缺乏标志物。取而代之的是，几乎所有的人类实验都是在体外用单核细胞产生的DC进行的，这些细胞只不完全反映原始DC。最近，我们鉴定了一种亚群特异性DC表面分子(XCR1受体)，树突状细胞上的额外分子由他人定义。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类DC。在该项目中，我们打算完善目前对原代人类血树突状细胞抗原(交叉)提呈给T细胞的初步理解，并确定驻留在淋巴组织和外周器官中的人类DC的基本表型和免疫功能。这些信息将表明，在小鼠身上开发的概念是否也适用于人类DC在健康和(自身免疫性)疾病方面的情况。这些知识是我们和其他人未来开发新型疫苗的先决条件，在这种疫苗中，对肿瘤和细胞内病原体的细胞毒免疫是通过在体内直接靶向XCR1+DC来实现的。

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.