title: Co-Activation of Cultured Human Natural Killer Cells: Enhanced Function and Decreased Inhibition.
abstract: Natural killer (NK) cells are important immune effector cells that protect the organism against viral infections and cancer. The cytotoxic activity of NK cells is induced by the engagement of a number of different activating surface receptors and controlled by inhibitory receptors to ensure self-tolerance. Resting NK cells need to be co-activated by involvement of at least two distinct activating receptors in order to induce their functional activity. However, in cultured NK cells, which have been expanded in cytokines such as interleukin (IL)-2, the engagement of a single activating receptor may be sufficient to induce their function. Data demonstrated that also cultured NK cells may be co-activated by involvement of certain combinations of activating receptors. This co-activation results in enhanced activation of Vav-1 and ERK signaling pathways and produces greater degranulation. In addition to enhanced functionality, co-activation makes NK cells more resistant to the effect of inhibitory receptors, thereby inducing more potent and efficient NK cell responses.
authors.affiliation: a Leibniz Research Center for Working Environment and Human Factors (IfADo), TU Dortmund University , Dortmund , Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Urlaub
authors.affiliation: b Institute for Immunology, University Hospital Heidelberg , Germany.|c German Cancer Research Centre (DKFZ) Unit F010 , Heidelberg , Germany.
authors.forename: Rauf
authors.initials: R
authors.lastname: Bhat
authors.affiliation: b Institute for Immunology, University Hospital Heidelberg , Germany.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Messmer
authors.affiliation: a Leibniz Research Center for Working Environment and Human Factors (IfADo), TU Dortmund University , Dortmund , Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Watzl
mesh_terms: D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051567:Proto-Oncogene Proteins c-vav; D055607:Receptors, Natural Killer Cell; C496618:VAV1 protein, human