Human blood MAIT cell subsets defined using MR1 tetramers

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Gherardin, NA; Souter, MNT; Koay, H-F; Mangas, KM; Seemann, T; Stinear, TP; Eckle, SBG; Berzins, SP; d'Udekem, Y; Konstantinov, IE; ...Date
2018-05-01Source Title
IMMUNOLOGY AND CELL BIOLOGYPublisher
WILEYUniversity 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 RadiologyMedicine (RMH)
Paediatrics (RCH)
Microbiology and Immunology
Sir Peter MacCallum Department of Oncology
Chancellery Research
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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 AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446826ARC Grant code
ARC/DE170100407Abstract
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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