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dc.contributor.authorKumashie, Kingsley Gideon
dc.contributor.authorCebula, Marcin
dc.contributor.authorHagedorn, Claudia
dc.contributor.authorKreppel, Florian
dc.contributor.authorPils, Marina C
dc.contributor.authorKoch-Nolte, Friedrich
dc.contributor.authorRissiek, Björn
dc.contributor.authorWirth, Dagmar
dc.date.accessioned2021-03-23T16:36:59Z
dc.date.available2021-03-23T16:36:59Z
dc.date.issued2021-02-03
dc.identifier.citationFront Immunol. 2021 Feb 3;11:592328. doi: 10.3389/fimmu.2020.592328.en_US
dc.identifier.pmid33613516
dc.identifier.doi10.3389/fimmu.2020.592328
dc.identifier.urihttp://hdl.handle.net/10033/622789
dc.description.abstractChronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCXCR5+ T cellsen_US
dc.subjectCpG oligonucleotideen_US
dc.subjectT cell exhaustionen_US
dc.subjectT cell reinvigorationen_US
dc.subjectexhausted stem-like T cellsen_US
dc.subjectfollicular helper-like T cellsen_US
dc.subjectliveren_US
dc.subjectliver resident T cellsen_US
dc.titleImproved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation.en_US
dc.typeArticleen_US
dc.identifier.eissn1664-3224
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in immunologyen_US
dc.source.volume11
dc.source.beginpage592328
dc.source.endpage
refterms.dateFOA2021-03-23T16:37:00Z
dc.source.journaltitleFrontiers in immunology
dc.source.countrySwitzerland


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