Abstracts (complete list) - Wissenschaft Online

Christoph D. Brenner, Susan King, Imke Wolters, Georg Bornkamm, Martin Röcken,
Ralph Mocikat
Tumour control by natural killer cells in a spontaneous mouse
lymphoma model
We have previously shown that downregulation of MHC class I provides a “danger”
signal that alerts the immune system resulting in target cell rejection and T-cell
memory. Injection of MHC class I-low target cells activated natural killer (NK) cells
thereby instructing dendritic cells to express IL-12 and to prime cytotoxic T
lymphocytes (CTL). This “cross-priming” could explain the rapid induction of T-cell
responses against viruses but left unanswered the question as to why this NK-cell help
is apparently not effective enough to convey protective CTL responses against MHC
class I-modulated autochthonous tumours. In the present study we used c-myctransgenic
mice, which spontaneously develop B-cell lymphomas by the age of 12
weeks, and studied the impact of tumour progression on the tumour reactivity of NK
cells. Activation markers of NK cells were elevated after onset of tumour growth and
clearly correlated with MHC class I downregulation of the developing tumours.
Nonetheless, NK cells isolated from tumour-bearing animals were not capable of lysing
tumour cells in vitro, and this was associated with reduced expression of several surface
markers such as CD49b. Most interestingly, tumour growth could be delayed if NK cells
received additional stimuli in vivo by treating mice with NK-cell-activating reagents. This
indicates that NK cells indeed play a role in controlling growth of spontaneous
lymphoma.