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dc.contributor.authorDias, J
dc.contributor.authorBoulouis, C
dc.contributor.authorGorin, J-B
dc.contributor.authorvan den Biggelaar, RHGA
dc.contributor.authorLal, KG
dc.contributor.authorGibbs, A
dc.contributor.authorLoh, L
dc.contributor.authorGulam, MY
dc.contributor.authorSia, WR
dc.contributor.authorBari, S
dc.contributor.authorHwang, WYK
dc.contributor.authorNixon, DF
dc.contributor.authorNguyen, S
dc.contributor.authorBetts, MR
dc.contributor.authorBuggert, M
dc.contributor.authorEller, MA
dc.contributor.authorBroliden, K
dc.contributor.authorTjernlund, A
dc.contributor.authorSandberg, JK
dc.contributor.authorLeeansyah, E
dc.date.accessioned2020-12-09T23:45:21Z
dc.date.available2020-12-09T23:45:21Z
dc.date.issued2018-12-04
dc.identifierpii: 1812273115
dc.identifier.citationDias, J., Boulouis, C., Gorin, J. -B., van den Biggelaar, R. H. G. A., Lal, K. G., Gibbs, A., Loh, L., Gulam, M. Y., Sia, W. R., Bari, S., Hwang, W. Y. K., Nixon, D. F., Nguyen, S., Betts, M. R., Buggert, M., Eller, M. A., Broliden, K., Tjernlund, A., Sandberg, J. K. & Leeansyah, E. (2018). The CD4-CD8- MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+ MAIT cell pool.. Proc Natl Acad Sci U S A, 115 (49), pp.E11513-E11522. https://doi.org/10.1073/pnas.1812273115.
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/11343/253315
dc.description.abstractMucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the MHC class I-like protein MR1. Human MAIT cells predominantly express the CD8α coreceptor (CD8+), with a smaller subset lacking both CD4 and CD8 (double-negative, DN). However, it is unclear if these two MAIT cell subpopulations distinguished by CD8α represent functionally distinct subsets. Here, we show that the two MAIT cell subsets express divergent transcriptional programs and distinct patterns of classic T cell transcription factors. Furthermore, CD8+ MAIT cells have higher levels of receptors for IL-12 and IL-18, as well as of the activating receptors CD2, CD9, and NKG2D, and display superior functionality following stimulation with riboflavin-autotrophic as well as riboflavin-auxotrophic bacterial strains. DN MAIT cells display higher RORγt/T-bet ratio, and express less IFN-γ and more IL-17. Furthermore, the DN subset displays enrichment of an apoptosis gene signature and higher propensity for activation-induced apoptosis. During development in human fetal tissues, DN MAIT cells are more mature and accumulate over gestational time with reciprocal contraction of the CD8+ subset. Analysis of the T cell receptor repertoire reveals higher diversity in CD8+ MAIT cells than in DN MAIT cells. Finally, chronic T cell receptor stimulation of CD8+ MAIT cells in an in vitro culture system supports the accumulation and maintenance of the DN subpopulation. These findings define human CD8+ and DN MAIT cells as functionally distinct subsets and indicate a derivative developmental relationship.
dc.languageeng
dc.publisherProceedings of the National Academy of Sciences
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleThe CD4-CD8- MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+ MAIT cell pool.
dc.typeJournal Article
dc.identifier.doi10.1073/pnas.1812273115
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titleProceedings of the National Academy of Sciences of USA
melbourne.source.volume115
melbourne.source.issue49
melbourne.source.pagesE11513-E11522
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1360496
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298106
melbourne.contributor.authorLoh, Liyen
dc.identifier.eissn1091-6490
melbourne.accessrightsOpen Access


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