Abstracts (complete list) - Wissenschaft Online

Veronika Lukacs-Kornek, Verena Semmling, Christian Kurts
Influence of Cross-Presentation via CCR7
Cross-presentation of extracellular antigens plays an important role in inducing
cytotoxic immune responses against bacteria and viruses, as well as in maintaining CD8
T cell tolerance against self antigens. It requires cellular contact between several rare
immune cells, such as specific CD8 T cells, specific CD4 T cells and cross-presenting
dendritic cells. Such encounters are usually regulated by chemokines and their
receptors. These mediators can guide immunocytes towards one destination, where
their encounters become more likely or can affect cellular function important in cross
priming. In the present study, we describe a role of a chemokine, CCL19, which signals
through CCR7, in cross-presentation.
Using CCR7-deficient mice we demonstrated that CCR7 decreased activation of CD8 T
cells by cross priming of cell-associated and of soluble antigens in vivo. To identify the
cells affected by CCR7 ligands during cross-presentation, we established an in vitro
cross-presentation assay. We could show that addition of CCL19 to the culture resulted
in increased cross-presentation, as evidenced by higher expression of early activation
markers such as CD69 and CD25 and elevated amounts of IL-2 produced by specific
CD8 T cells. CCR7 did not affect the antigen uptake capacity of dendritic cells (DC) in
vitro. Furthermore, selective CCR7-deficiency in DC did not prevent the stimulatory
effect of CCL19 on CD8 T cell activation. However, this effect was completely abolished
when CCR7-/- CD8 T cells were used. Therefore the increased activation of CD8 T cells
during cross-presentation was exclusively mediated by a direct effect of CCL19 on the
CD8 T cells. Future efforts are aimed identifying the intracellular mechanisms employed
by CCL19 to stimulate CD8 T cells.