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    Human blood MAIT cell subsets defined using MR1 tetramers

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    Author
    Gherardin, NA; Souter, MNT; Koay, H-F; Mangas, KM; Seemann, T; Stinear, TP; Eckle, SBG; Berzins, SP; d'Udekem, Y; Konstantinov, IE; ...
    Date
    2018-05-01
    Source Title
    IMMUNOLOGY AND CELL BIOLOGY
    Publisher
    WILEY
    University of Melbourne Author/s
    Neeson, Paul; Souter, Michael; Seemann, Torsten; Eckle, Sidonia; Berzins, Stuart; D'Udekem D'Acoz, Yves; Ritchie, David; Pellicci, Daniel; Uldrich, Adam; Godfrey, Dale; ...
    Affiliation
    Medicine and Radiology
    Medicine (RMH)
    Paediatrics (RCH)
    Microbiology and Immunology
    Sir Peter MacCallum Department of Oncology
    Chancellery Research
    Metadata
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    Document Type
    Journal Article
    Citations
    Gherardin, N. A., Souter, M. N. T., Koay, H. -F., Mangas, K. M., Seemann, T., Stinear, T. P., Eckle, S. B. G., Berzins, S. P., d'Udekem, Y., Konstantinov, I. E., Fairlie, D. P., Ritchie, D. S., Neeson, P. J., Pellicci, D. G., Uldrich, A. P., McCluskey, J. & Godfrey, D. I. (2018). Human blood MAIT cell subsets defined using MR1 tetramers. IMMUNOLOGY AND CELL BIOLOGY, 96 (5), pp.507-525. https://doi.org/10.1111/imcb.12021.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/229632
    DOI
    10.1111/imcb.12021
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446826
    ARC Grant code
    ARC/DE170100407
    Abstract
    Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18Rα and CD26. The development of MR1-Ag tetramers now permits the specific identification of MAIT cells based on T-cell receptor specificity. Here, we compare these approaches for identifying MAIT cells and show that surrogate markers are not always accurate in identifying these cells, particularly the CD4+ fraction. Moreover, while all MAIT cell subsets produced comparable levels of IFNγ, TNF and IL-17A, the CD4+ population produced more IL-2 than the other subsets. In a human ontogeny study, we show that the frequencies of most MR1 tetramer+ MAIT cells, with the exception of CD4+ MAIT cells, increased from birth to about 25 years of age and declined thereafter. We also demonstrate a positive association between the frequency of MAIT cells and other unconventional T cells including Natural Killer T (NKT) cells and Vδ2+ γδ T cells. Accordingly, this study demonstrates that MAIT cells are phenotypically and functionally diverse, that surrogate markers may not reliably identify all of these cells, and that their numbers are regulated in an age-dependent manner and correlate with NKT and Vδ2+ γδ T cells.

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