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dc.contributor.authorVerma, Kriti
dc.contributor.authorCroft, Wayne
dc.contributor.authorMargielewska-Davies, Sandra
dc.contributor.authorPearce, Hayden
dc.contributor.authorStephens, Christine
dc.contributor.authorDiaconescu, Diana
dc.contributor.authorBevington, Sarah
dc.contributor.authorCraddock, Charles
dc.contributor.authorAmel-Kashipaz, Rasoul
dc.contributor.authorZuo, Jianmin
dc.contributor.authorKinsella, Francesca A M
dc.contributor.authorMoss, Paul
dc.date.accessioned2024-11-26T16:32:46Z
dc.date.available2024-11-26T16:32:46Z
dc.date.issued2024-09-24
dc.identifier.citationVerma K, Croft W, Margielewska-Davies S, Pearce H, Stephens C, Diaconescu D, Bevington S, Craddock C, Amel-Kashipaz R, Zuo J, Kinsella FAM, Moss P. CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD. Blood Adv. 2024 Sep 24;8(18):4900-4912. doi: 10.1182/bloodadvances.2024012909.en_US
dc.identifier.issn2473-9529
dc.identifier.eissn2473-9537
dc.identifier.doi10.1182/bloodadvances.2024012909
dc.identifier.pmid39028952
dc.identifier.urihttp://hdl.handle.net/20.500.14200/6605
dc.description.abstractGraft-versus-host disease (GVHD) remains a major challenge after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and further understanding of its immunopathology is crucial for developing new treatments. CD70 interacts with CD27 and is upregulated transiently on T cells after recent T-cell receptor (TCR) engagement. Here, we investigated the functional and clinical significance of CD70 expression on T cells during the early posttransplantation period. CD70 was expressed on a subset of highly activated memory T cells within the first 2 weeks after transplant, which then gradually declined in most patients. CD70+ T cells exhibited an open chromatin landscape and a transcriptional profile indicative of intense Myelocytomatosis oncogene (MYC)-driven glycolysis and proliferation. CD4+ and CD8+CD70+ T-cell numbers increased by ninefold and fourfold, respectively, during acute GVHD (aGVHD) and displayed an oligoclonal TCR repertoire. These cells expressed CCR4 and CCR6 chemokine receptors and were markedly increased in aGVHD tissue samples. Furthermore, CD70+ T cells demonstrated alloreactive specificity in vitro, and proliferative and inflammatory cytokine responses were markedly attenuated by CD70 blockade. These findings identify CD70 as a marker of highly activated alloreactive T cells and reveal the potential therapeutic importance of inhibiting CD27-CD70 costimulation in both the prophylaxis and treatment of aGVHD.en_US
dc.language.isoenen_US
dc.publisherAmerican Society of Hematologyen_US
dc.relation.urlhttps://ashpublications.org/bloodadvancesen_US
dc.rights© 2024 by The American Society of Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.subjectHaematologyen_US
dc.titleCD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.source.journaltitleBlood Advancesen_US
dc.source.volume8
dc.source.issue18
dc.source.beginpage4900
dc.source.endpage4912
dc.source.countryUnited States
rioxxterms.versionNAen_US
dc.contributor.trustauthorCraddock, Charles
dc.contributor.trustauthorAmel-Kashipaz, Rasoul
dc.contributor.trustauthorKinsella, Francesca
dc.contributor.trustauthorMoss, Paul
dc.contributor.departmentHaematologyen_US
dc.contributor.departmentHistopathologyen_US
dc.contributor.roleAdmin and Clericalen_US
dc.contributor.roleMedical and Dentalen_US
oa.grant.openaccessnaen_US


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