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dc.contributor.authorMcCarthy, NE
dc.contributor.authorBashir, Z
dc.contributor.authorVossenkämper, A
dc.contributor.authorHedin, CR
dc.contributor.authorGiles, EM
dc.contributor.authorBhattacharjee, S
dc.contributor.authorBrown, SG
dc.contributor.authorSanders, TJ
dc.contributor.authorWhelan, K
dc.contributor.authorMacDonald, TT
dc.contributor.authorLindsay, JO
dc.contributor.authorStagg, AJ
dc.date.accessioned2014-01-29T11:27:10Z
dc.date.issued2013-09-01
dc.date.issued2013-09-01
dc.date.issued2013-09-01
dc.identifier.citationMcCarthy, N., Bashir, Z., Vossenkamper, A., Hedin, C., Giles, E., Bhattacharjee, S., Brown, S., Sanders, T., Whelan, K., MacDonald, T., Lindsay, J. and Stagg, A. (2013). Proinflammatory V 2+ T Cells Populate the Human Intestinal Mucosa and Enhance IFN-  Production by Colonic    T Cells. [online] The Journal of Immunology. Available at: http://www.jimmunol.org/content/191/5/2752 [Accessed 6 Dec. 2017].
dc.identifier.urihttp://qmro.qmul.ac.uk/jspui/handle/123456789/5470
dc.description.abstractIn nonhuman primates, Vγ9Vδ2(+) (Vδ2)T cells proliferate and accumulate in mucosal tissues following microbial activation. Human Vδ2T cells produce proinflammatory cytokines in response to bacterial species that colonize the gut, but the role played by Vδ2T cells in intestinal immunity is unknown. We hypothesized that circulating Vδ2T cells can populate the human intestine and contribute to mucosal inflammation. Cell suspensions prepared from peripheral blood and intestinal biopsies were stimulated with microbial phosphoantigen (1-hydroxy-2-methyl-2-buten-4-yl 4-diphosphate [HDMAPP]) and analyzed by flow cytometry to determine Vδ2T cell phenotype, cytokine production, and proliferative potential. Circulating Vδ2T cells expressed gut-homing integrin α4β7 (>70%), which was coexpressed with skin-associated cutaneous leukocyte Ag by up to 15% of the total population. However, Vδ2T cell activation with HDMAPP and exposure to retinoic acid (signaling via retinoic acid receptor α) increased α4β7 expression and enhanced binding to mucosal addressin cell adhesion molecule-1 in vitro while simultaneously suppressing cutaneous leukocyte Ag, thereby generating a committed gut-tropic phenotype. Confocal microscopy and flow cytometry identified frequent Vδ2T cells that migrated out of human intestinal biopsies and comprised both CD103(+) and CD103(-) subsets that produced TNF-α and IFN-γ upon phosphoantigen exposure, with more frequent cytokine-producing cells in the CD103(-) population. Activated intestinal Vδ2T cells expressed CD70 and HLA-DR but were unable to drive the proliferation of allogeneic naive CD4(+) T cells. Instead, phosphoantigen-activated CD103(-) Vδ2T cells increased T-bet expression and enhanced IFN-γ production by autologous colonic αβ T cells via an IFN-γ-dependent mechanism. These data demonstrate that circulating Vδ2T cells display enhanced gut-homing potential upon microbial activation and populate the human intestinal mucosa, generating functionally distinct CD103(+) and CD103(-) subsets that can promote inflammation by colonic αβ T cells.
dc.format.extent2752 - 2763
dc.languageeng
dc.subjectFlow Cytometry
dc.subjectHumans
dc.subjectInterferon-gamma
dc.subjectIntestinal Mucosa
dc.subjectLymphocyte Culture Test, Mixed
dc.subjectMicroscopy, Confocal
dc.subjectPhenotype
dc.subjectReceptors, Antigen, T-Cell, gamma-delta
dc.subjectT-Lymphocyte Subsets
dc.titleProinflammatory Vδ2+ T cells populate the human intestinal mucosa and enhance IFN-γ production by colonic αβ T cells.
dc.typeJournal Article
dc.rights.holderCopyright © 2013 by The American Association of Immunologists, Inc.
dc.identifier.doi10.4049/jimmunol.1202959
dc.relation.isPartOfJ Immunol
dc.relation.isPartOfJ Immunol
pubs.author-urlhttp://www.ncbi.nlm.nih.gov/pubmed/23904167
pubs.issue5
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Immunobiology
pubs.publication-statusPublished
pubs.volume191


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