Identification of phenotypically and functionally heterogeneous mouse Mucosal Associated Invariant T cells using MR1 tetramers. — ASN Events
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Identification of phenotypically and functionally heterogeneous mouse Mucosal Associated Invariant T cells using MR1 tetramers. (#116)

Hui-Fern Koay 1 2 , Azad Rahimpour 1 , Anselm Enders 3 , Rhiannon Clanchy 1 , Sidonia Eckle 1 , Bronwyn Meehan 1 , Zhenjun Chen 1 , Belinda Whittle 4 , Ligong Liu 5 6 , David Fairlie 5 6 , Chris Goodnow 3 , James McCluskey 1 , Jamie Rossjohn 7 8 9 , Adam Uldrich 1 2 , Daniel Pellicci 1 2 , Dale Godfrey 1 2
  1. Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia
  2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, Australia
  3. Department of Immunology, John Curtin School of Medical Research, Canberra, ACT, Australia
  4. Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
  5. Institute for Molecular Bioscience, , University of Queensland,, Brisbane, , QLD, Australia
  6. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Queensland, Brisbane, QLD, Australia
  7. Departent of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  8. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK
  9. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia

Studies on the biology of Mucosal-Associated Invariant T (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 CD44hiCD62Llo memory phenotype and produced high levels of IL-17A, and other cytokines including IFN-g, IL-4, IL-10, IL-13, GM-CSF at moderate levels. Consistent with high IL-17A production, most MAIT cells expressed high levels of retinoic-acid-related orphan receptor (ROR)gt, whereas RORgtlo MAIT cells predominantly expressed T-bet and produced IFN-g. Most MAIT cells expressed the promyelocytic leukaemia zinc finger (PLZF) transcription factor and their development was largely PLZF-dependent. These observations contrasted with previous reports that MAIT cells from Va19 TCR transgenic mice were PLZF- and expressed a naïve CD44lo 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.