|Title:||The regulation of NK cell detachment from target cells as a key factor for serial killing and effector function|
|Abstract:||Natural Killer cells efficiently recognize and kill infected or malignant cells and can eliminate several of these cells one after the other in a process called serial killing. The activation of NK cells and how they form conjugates with target cells is well studied, but for the efficient killing of multiple cells, NK cells also have to detach from the previous target cell. The process of detachment is still poorly understood; therefore analyzing the regulation of this process in more detail is important for the investigation of NK cell biology. I used flow cytometry based assays to analyze the adhesion and the detachment of NK cells and target cells. The data show, that the detachment was different between fresh, IL-2 activated and cultured NK cells while the formation of conjugates was almost unchanged. Interestingly, blocking NK cell cytotoxicity inhibited detachment. Reducing target cell death by increasing their resistance against NK cells also reduced the detachment of NK cells and increased the production of the cytokines IFN-γ and TNF-α. Induction of NK cell independent target cell death had the opposite effect. The loss of ligands for activating NK cell receptors and the majority of adhesion molecules on the target cell membrane during cell death could be responsible for the NK cell detachment. Additionally, NK cells seem to sense soluble factors released by dying cells, like apoptotic bodies, which accelerated the detachment. This demonstrates, that the detachment of NK cells is a highly regulated process, which depends on the activation status of the NK cell, ongoing receptor-ligand interactions and changes in the protein profile of the cell membrane after death of the target cell. Regulation of detachment is not only necessary for the efficiency of serial killing but also influences other NK cell effector functions like cytokine production.|
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