Abstracts (complete list) - Wissenschaft Online

Eva Rieser, Monika Braun, Barbara Simm, Barbara Mosetter, Christine S. Falk
Differences between cytotoxicity and cytokine expression are
due to different phosphorylation patterns
Introduction: The plasticity of human natural killer cells is reflected by the individual
expression pattern of activating as well as inhibitory receptors. Besides this receptor
expression, the amplitude of activity is determined by the intracellular signaling status.
Previous studies have shown that NK cells expressing a similar receptor repertoire do
not necessarily resemble identical activity regarding cytotoxicity and cytokine
expression. Therefore, the differences in the intracellular signaling status of each NK cell
may influence its reactivity to receptor-mediated triggering. Presuming that
dysfunctions in different signaling cascades might explain the hyporeactivity of certain
NK cells, we analyzed the intracellular phosphorylation patterns in response to various
stimuli. We used several NK lines that differ in cytotoxicity and cytokine secretion,
respectively.
Materials and methods: Three NK lines were compared regarding cytotoxicity (CD107a
degranulation) and cytokine secretion (multiplex technology). Phosphorylation patterns
following PMA/ionomycin and receptor-mediated stimulation were determined by
phosphoplex analysis quantifying total amounts of more than 10 kinases and their
phosphorylated proportions.
Results: Substantial differences were observed in their individual cytolytic activity and
cytokine secretion pattern. In addition to these functional differences, the
phophorylation status and the overall amount of signaling molecules also varied
substantially between these NK lines. Our results implicate a correlation between low
cytotoxic activity a special set of cytokine production and less phosphorylation for most
of the tested signaling proteins. Therefore, receptor expression alone is not sufficient for
NK function because the kinase compositions and the phosphorylation cascades
determine the individual reactivity and, thus, plasticity of NK cells.