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

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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.