Abstracts (complete list) - Wissenschaft Online

Mathias Lucas, William Schachterle, Karin Oberle, Peter Aichele, Andreas Diefenbach
Dendritic Cells Prime Natural Killer Cells
by trans-Presenting Interleukin 15
Natural killer (NK) cells are lymphocytes of the rapidly acting innate immune system
that play an essential role in the recognition and eradication of virally infected cells and
tumors. Recent in vitro data suggested that dendritic cells (DC)- or macrophage-derived
cytokines are able to enhance NK cell functions. However, it is unknown if NK cell
effector responses in vivo depend on the NK cells’ interaction with myeloid cells. Using a
mouse model for the inducible ablation of DC, we show that the in vivo priming of NK
cell responses to viral and bacterial pathogens depended on the presence of CD11c high
DCs. After peripheral Toll-like receptor (TLR) stimulation, priming of NK cells required
their recruitment to local lymph nodes and interaction with DCs resulting in the
emergence of effector NK cells in the periphery. NK cell priming was dependent on the
recognition of type I IFN signals by DCs and the subsequent production and transpresentation
of IL-15 by DCs to resting NK cells. CD11c high DC-derived IL-15 was
necessary and sufficient for the priming of NK cells. Our data define a unique in vivo
role of DC for the priming of NK cells, revealing a striking and previously unappreciated
homology to T lymphocytes of the adaptive immune system. These results have
important implications for the development of immunotherapeutic strategies aiming to
boost NK cell effector