title: NKp46 defines ovine cells that have characteristics corresponding to NK cells.
abstract: Natural killer (NK) cells are well recognized as playing a key role in innate immune defence through cytokine production and cytotoxic activity; additionally recent studies have identified several novel NK cell functions. The ability to study NK cells in the sheep has been restricted due to a lack of specific reagents. We report the generation of a monoclonal antibody specific for ovine NKp46, a receptor which in a number of mammals is expressed exclusively in NK cells. Ovine NKp46+ cells represent a population that is distinct from CD4+ and γδ+ T-cells, B-cells and cells of the monocytic lineage. The NKp46+ cells are heterogenous with respect to expression of CD2 and CD8 and most, but not all, express CD16--characteristics consistent with NK cell populations in other species. We demonstrate that in addition to populations in peripheral blood and secondary lymphoid organs, ovine NKp46+ populations are also situated at the mucosal surfaces of the lung, gastro-intestinal tract and non-gravid uterus. Furthermore, we show that purified ovine NKp46+ populations cultured in IL-2 and IL-15 have cytotoxic activity that could be enhanced by ligation of NKp46 in re-directed lysis assays. Therefore we conclude that ovine NKp46+ cells represent a population that by phenotype, tissue distribution and function correspond to NK cells and that NKp46 is an activating receptor in sheep as in other species.
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, Edinburgh, Scotland, EH25 9RG, UK. timothy.connelley@ed.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Connelley
authors.forename: Anne K
authors.initials: AK
authors.lastname: Storset
authors.forename: Alan
authors.initials: A
authors.lastname: Pemberton
authors.forename: Niall
authors.initials: N
authors.lastname: MacHugh
authors.forename: Jeremy
authors.initials: J
authors.lastname: Brown
authors.forename: Hege
authors.initials: H
authors.lastname: Lund
authors.forename: Ivan W
authors.initials: IW
authors.lastname: Morrison
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques / Q000662:veterinary; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012756:Sheep / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D055627:Natural Cytotoxicity Triggering Receptor 1; D011994:Recombinant Proteins