Abstracts (complete list) - Wissenschaft Online

Kerstin Annika Sauer, Joachim Heinrich Maxeiner, Petra Scholtes, Roman Karwot,
Hans-Anton Lehr, Mark Birkenbach, Richard Steven Blumberg, Susetta Finotto
Immunosurveillance of lung melanoma metastasis in EBI-3
(-/-) mice by NK-DCs- induced CD8+ T cells
Antigen presentation plays an important role in lung metastasis, although the
immunological mechanisms are not completely understood. Epstein-Barr virus-induced
gene 3 codes for a soluble type 1 receptor homologous to the p40 subunit of IL-12 that
is expressed by antigen presenting cells following activation. Adoptive intravenous
injection of the B16-F10 cell line resulted in a significant reduction of lung tumor
metastasis in EBI-3 (-/-) recipient mice compared to wild type. Consistently, we found
that EBI-3 (-/-) mice had decreased number of VCAM-1+ endothelial cells. The
immunological finding accompanying this therapeutic effect was the orchestrate priming
and activation of T cells by a newly described Dendritic Cell (DC) subset called Natural
Killer Dendritic Cells (NK-DC). NK-DCs from EBI-3 (-/-) mice released increased
amounts of IFN-gamma thereby inducing augmented CD8+ T cell responses in the lung.
This in turn resulted in a TNF-alpha-TRAIL mediated programmed cell death of local
metastatic tumor cells in the lung of EBI-3 deficient mice. Finally, adoptive transfer of
EBI-3 (-/-) NK-DC primed CD8+ T cells into tumor bearing wild-type mice ameliorated
the development of lung metastasis in recipient mice. Taken together, these data
demonstrate that EBI-3 is a crucial regulator of anti-tumor CD8+ T cell responses in the
lung by controlling NK-DC activity.
This work is funded by the Graduiertenkolleg 1043 and Immuno-intervention Cluster of
Excellence (ICE, Mainz, Germany).