title: Regulation of human NK-cell cytokine and chemokine production by target cell recognition.
abstract: Natural killer (NK)-cell recognition of infected or neoplastic cells can induce cytotoxicity and cytokine secretion. So far, it has been difficult to assess the relative contribution of multiple NK-cell activation receptors to cytokine and chemokine production upon target cell recognition. Using Drosophila cells expressing ligands for the NK-cell receptors LFA-1, NKG2D, DNAM-1, 2B4, and CD16, we studied the minimal requirements for secretion by freshly isolated, human NK cells. Target cell stimulation induced secretion of predominately proinflammatory cytokines and chemokines. Release of chemokines MIP-1alpha, MIP-1beta, and RANTES was induced within 1 hour of stimulation, whereas release of TNF-alpha and IFN-gamma occurred later. Engagement of CD16, 2B4, or NKG2D sufficed for chemokine release, whereas induction of TNF-alpha and IFN-gamma required engagement of additional receptors. Remarkably, our results revealed that, upon target cell recognition, CD56(dim) NK cells were more prominent cytokine and chemokine producers than CD56(bright) NK cells. The present data demonstrate how specific target cell ligands dictate qualitative and temporal aspects of NK-cell cytokine and chemokine responses. Conceptually, the results point to CD56(dim) NK cells as an important source of cytokines and chemokines upon recognition of aberrant cells, producing graded responses depending on the multiplicity of activating receptors engaged.
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. cfauriat@wanadoo.fr
authors: Cyril
authors: C
authors: Fauriat
authors: Eric O
authors: EO
authors: Long
authors: Hans-Gustaf
authors: HG
authors: Ljunggren
authors: Yenan T
authors: YT
authors: Bryceson
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D008024:Ligands; D018448:Models, Immunological; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019002:CD56 Antigen; D018925:Chemokines; D018836:Inflammation Mediators; D020382:Interleukin-18; D008024:Ligands; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D018664:Interleukin-12