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dc.contributor.authorCosgrove, Cormac
dc.contributor.authorBerger, Christoph T.
dc.contributor.authorKroy, Daniela C.
dc.contributor.authorCheney, Patrick C.
dc.contributor.authorGhebremichael, Musie
dc.contributor.authorAneja, Jasneet
dc.contributor.authorTomlinson, Michelle
dc.contributor.authorKim, Arthur Y.
dc.contributor.authorLauer, Georg M.
dc.contributor.authorAlter, Galit
dc.date.accessioned2014-10-20T12:29:51Z
dc.date.available2014-10-20T12:29:51Z
dc.date.issued2014-08
dc.date.submitted2014-03
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/90975
dc.description.abstractAlthough epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56[superscript bright] NK cell population, which produced less IFNγ and CD107a but comparable levels of MIP1β, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161[superscript low]perforin[superscript high] NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant U19 #AI08230)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant U19 #AI066345)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0105950en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePublic Library of Scienceen_US
dc.titleChronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liveren_US
dc.typeArticleen_US
dc.identifier.citationCosgrove, Cormac, Christoph T. Berger, Daniela C. Kroy, Patrick C. Cheney, Musie Ghebremichael, Jasneet Aneja, Michelle Tomlinson, Arthur Y. Kim, Georg M. Lauer, and Galit Alter. “Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More Than in the Liver.” Edited by Naglaa H. Shoukry. PLoS ONE 9, no. 8 (August 22, 2014): e105950.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentRagon Institute of MGH, MIT and Harvarden_US
dc.contributor.mitauthorAlter, Galiten_US
dc.relation.journalPLoS ONEen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCosgrove, Cormac; Berger, Christoph T.; Kroy, Daniela C.; Cheney, Patrick C.; Ghebremichael, Musie; Aneja, Jasneet; Tomlinson, Michelle; Kim, Arthur Y.; Lauer, Georg M.; Alter, Galiten_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1570-9445
mit.licensePUBLISHER_CCen_US


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