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dc.contributor.authorSchurich, Annaen
dc.contributor.authorPallett, Laura Jen
dc.contributor.authorJajbhay, Danyalen
dc.contributor.authorWijngaarden, Jessicaen
dc.contributor.authorOtano, Itziaren
dc.contributor.authorGill, Upkar Sen
dc.contributor.authorHansi, Navjyoten
dc.contributor.authorKennedy, Patrick Ten
dc.contributor.authorNastouli, Elenien
dc.contributor.authorGilson, Richarden
dc.contributor.authorFrezza, Christianen
dc.contributor.authorHenson, Sian Men
dc.contributor.authorMaini, Mala Ken
dc.date.accessioned2016-07-20T08:56:27Z
dc.date.available2016-07-20T08:56:27Z
dc.date.issued2016-07-21en
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/256782
dc.description.abstractT cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1hi T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1hi HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV)-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL)-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.
dc.description.sponsorshipA.S., J.W., and M.K.M. are funded by a Wellcome Trust Senior Investigator Award (to M.K.M.); L.J.P. and M.K.M. are funded by MRC Project grant no. MR/M020126/; I.O. is funded by an EASL post-doctoral fellowship; U.S.G. is funded by the Wellcome Trust Clinical Research Training Fellowship; and N.H. and P.T.K. are funded by a grant from Barts and The London Charity. A.S. was also funded by a UCLH CIDC/NIHR Fast Track Grant, and D.J. was funded by the Wolfson Foundation.
dc.languageEnglishen
dc.language.isoenen
dc.publisherElsevier (Cell Press)
dc.rightsAttribution 4.0 International*
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleDistinct metabolic requirements of exhausted and functional virus-specific CD8 T cells in the same hosten
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.celrep.2016.06.078en
prism.publicationDate2016en
prism.publicationNameCell Reportsen
dc.identifier.doi10.17863/CAM.721
dcterms.dateAccepted2016-06-17en
rioxxterms.versionofrecord10.1016/j.celrep.2016.06.078en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-07-21en
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12022/1_do not transfer?)
pubs.funder-project-idMedical Research Council (MC_UU_12022/6)
cam.orpheus.successThu Jan 30 12:57:34 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International