title: Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers.
abstract: Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor γt (RORγt), whereas RORγt(lo) MAIT cells predominantly express T-bet and produce IFN-γ. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Azad
authors.initials: A
authors.lastname: Rahimpour
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Hui Fern
authors.initials: HF
authors.lastname: Koay
authors.affiliation: Department of Immunology and Infectious Disease and Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Anselm
authors.initials: A
authors.lastname: Enders
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Clanchy
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Sidonia B G
authors.initials: SB
authors.lastname: Eckle
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Meehan
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Immunology and Infectious Disease and Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Whittle
authors.affiliation: Institute for Molecular Bioscience and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia Institute for Molecular Bioscience and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Ligong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute for Molecular Bioscience and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia Institute for Molecular Bioscience and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.affiliation: Department of Immunology and Infectious Disease and Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia godfrey@unimelb.edu.au.
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006652:Histological Techniques; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000166:cytology / Q000378:metabolism*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D051741:Kruppel-Like Transcription Factors; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell; C513267:Zbtb16 protein, mouse