title: IFN-gamma production and degranulation are differentially regulated in response to stimulation in murine natural killer cells.
abstract: Activation of natural killer (NK) cells is induced via receptors like NKG2D, NKR-P1C and NKp46. This activation is balanced by interactions with inhibitory receptors. NK cell activation can lead to cytotoxicity mediated via polarized exocytosis of secretory lysosomes (degranulation) and interferon (IFN)-gamma production. We studied cell surface mobilization of a molecule present in secretory lysosomes, CD107a (LAMP-1), to monitor the relationship between degranulation of NK cells and their production of IFN-gamma at the single cell level. A comparison of responses in naive mouse NK cells and NK cells pre-activated with the type I interferon-inducer tilorone demonstrated a dramatic influence of pre-activation, allowing potent degranulation and IFN-gamma responses to NKG2D mediated stimulation that were not observed with naive NK cells. Degranulation and IFN-gamma production were performed by overlapping NK cell populations with generally higher frequencies of degranulating than IFN-gamma producing NK cells. An NK cell subset analysis based on expression of Mac-1 and CD27 revealed that immature NK cells (Mac-1(lo) CD27(hi)) are preferentially degranulating, Mac-1(hi) CD27(hi) cells perform both effector functions efficiently, while the most mature (Mac-1(hi) CD27(lo)) NK cells display reduced degranulation but with maintained IFN-gamma production.
authors.affiliation: Department for Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Vahlne
authors.forename: S
authors.initials: S
authors.lastname: Becker
authors.forename: P
authors.initials: P
authors.lastname: Brodin
authors.forename: M H
authors.initials: MH
authors.lastname: Johansson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015550:Cell Degranulation / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell
chemical_list: D000911:Antibodies, Monoclonal; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma