Dynamic behavior of NK cells during activation in lymph nodes

Institut Pasteur, G5 Dynamiques des Réponses Immunes, Paris, France.
Blood (Impact Factor: 10.43). 09/2009; 114(15):3227-34. DOI: 10.1182/blood-2009-06-228759
Source: PubMed

ABSTRACT During infection, Toll-like receptor agonists induce natural killer (NK)-cell activation by stimulating dendritic cells (DCs) to produce cytokines and transpresent IL-15 to NK cells. Yet the cellular dynamics underlying NK-cell activation by DCs in secondary lymphoid organs are largely unknown. Here, we have visualized NK-cell activation using mice in which NK cells and DCs express different fluorescent proteins. In response to poly I:C or lipopolysaccharide, NK cells maintained a vigorous migratory behavior, establishing multiple short contacts with maturing DCs. Furthermore, mature antigen-loaded DCs that made long-lived interactions with T cells formed short-lived contacts with NK cells. The different behaviors of T cells and NK cells during activation was correlated with distinct calcium responses upon interaction with DCs. That NK cells become activated while remaining motile may constitute an efficient strategy for sampling local concentrations of cytokines around DCs in secondary lymphoid tissues.

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    • "These activating domains segregate from inhibitory domains that allow MHC class I/KIR interactions and form rapidly within the first minutes of mature DC interaction with NK cells. The rapid establishment of the immunological synapse between mature DCs and resting NK cells, which ensures NK-cell activation and DC protection from NK-cell cytotoxicity at the same time, seems to be important, because in vivo imaging has revealed that DCs and NK cells might only interact with each other in T-cell areas of secondary lymphoid tissues for short periods of time with the majority of contacts being around 1min [23] [24]. At these early time points, however, the synapse between DCs and NK cells is not stabilized by cytoskeletal components like actin. "
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