title: NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features.
abstract: The NKp46 receptor demonstrates a high degree of lineage specificity, being expressed almost exclusively in NK cells. Previous studies have demonstrated NKp46 expression by T cells, but NKp46+ CD3+ cells are rare and almost universally associated with NKp46 acquisition by T cells following stimulation. In this study we demonstrate the existence of a population of NKp46+ CD3+ cells resident in normal bovine PBMCs that includes cells of both the αβ TCR+ and γδ TCR+ lineages and is present at a frequency of 0.1-1.7%. NKp46+ CD3+ cells express transcripts for a broad repertoire of both NKRs and TCRs and also the CD3ζ, DAP10, and FcεR1γ but not DAP12 adaptor proteins. In vitro functional analysis of NKp46+ CD3+ cells confirm that NKp46, CD16, and CD3 signaling pathways are all functionally competent and capable of mediating/redirecting cytolysis. However, only CD3 cross-ligation elicits IFN-γ release. NKp46+ CD3+ cells exhibit cytotoxic activity against autologous Theileria parva-infected cells in vitro, and during in vivo challenge with this parasite an expansion of NKp46+ CD3+ cells was observed in some animals, indicating the cells have the potential to act as an anti-pathogen effector population. The results in this study identify and describe a novel nonconventional NKp46+ CD3+ T cell subset that is phenotypically and functionally distinct from conventional NK and T cells. The ability to exploit both NKRs and TCRs suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses.
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom;
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Connelley
authors.forename: Cassandra
authors.initials: C
authors.lastname: Longhi
authors.forename: Alison
authors.initials: A
authors.lastname: Burrells
authors.forename: Kathryn
authors.initials: K
authors.lastname: Degnan
authors.forename: Jayne
authors.initials: J
authors.lastname: Hope
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Allan
authors.forename: John A
authors.initials: JA
authors.lastname: Hammond
authors.forename: Anne K
authors.initials: AK
authors.lastname: Storset
authors.forename: W Ivan
authors.initials: WI
authors.lastname: Morrison
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000469:parasitology; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D016794:Theileria / Q000276:immunology; D013801:Theileriasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D055627:Natural Cytotoxicity Triggering Receptor 1; D011948:Receptors, Antigen, T-Cell; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma