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dc.contributor.authorMuñoz-Ruiz, M
dc.contributor.authorRibot, JC
dc.contributor.authorGrosso, AR
dc.contributor.authorGonçalves-Sousa, N
dc.contributor.authorPamplona, A
dc.contributor.authorPennington, DJ
dc.contributor.authorRegueiro, JR
dc.contributor.authorFernández-Malavé, E
dc.contributor.authorSilva-Santos, B
dc.date.accessioned2017-01-19T15:41:22Z
dc.date.issued2016-04-04
dc.date.issued2016-06
dc.date.submitted2016-11-16T18:01:08.378Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/18858
dc.description.abstractThe mouse thymus produces discrete γδ T cell subsets that make either interferon-γ (IFN-γ) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g(+/-) Cd3d(+/-) (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on γδ T cells. CD3DH mice had normal numbers and phenotypes of αβ thymocyte subsets, but impaired differentiation of fetal Vγ6(+) (but not Vγ4(+)) IL-17-producing γδ T cells and a marked depletion of IFN-γ-producing CD122(+) NK1.1(+) γδ T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-γ(+) γδ T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology.
dc.format.extent721 - 727
dc.languageeng
dc.language.isoenen_US
dc.relation.ispartofNat Immunol
dc.titleTCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.
dc.typeJournal Article
dc.rights.holder© 2016, Rights Managed by Nature Publishing Group
dc.identifier.doi10.1038/ni.3424
dc.relation.isPartOfNat Immunol
dc.relation.isPartOfNat Immunol
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/27043412
pubs.issue6
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/Immunology and Infectious Disease
pubs.publication-statusPublished
pubs.volume17


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