Show simple item record

dc.contributor.authorLeveque-El mouttie, Lucie
dc.contributor.authorKoyama, Motoko
dc.contributor.authorLe Texier, Laetitia
dc.contributor.authorMarkey, Kate A.
dc.contributor.authorCheong, Melody
dc.contributor.authorKuns, Rachel D.
dc.contributor.authorLineburg, Katie E.
dc.contributor.authorTeal, Bianca E.
dc.contributor.authorAlexander, Kylie A.
dc.contributor.authorClouston, Andrew D.
dc.contributor.authorBlazar, Bruce R.
dc.contributor.authorHill, Geoffrey R.
dc.contributor.authorMacDonald, Kelli P. A.
dc.date.accessioned2019-03-21T06:08:53Z
dc.date.available2019-03-21T06:08:53Z
dc.date.issued2016
dc.identifier.issn1528-0020
dc.identifier.doi10.1182/blood-2015-11-680876
dc.identifier.urihttp://hdl.handle.net/10072/124017
dc.description.abstractChronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society of Hematology
dc.relation.ispartofpagefrom794
dc.relation.ispartofpageto804
dc.relation.ispartofissue6
dc.relation.ispartofjournalBlood
dc.relation.ispartofvolume128
dc.subject.fieldofresearchCellular Immunology
dc.subject.fieldofresearchCardiorespiratory Medicine and Haematology
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchPaediatrics and Reproductive Medicine
dc.subject.fieldofresearchcode110704
dc.subject.fieldofresearchcode1102
dc.subject.fieldofresearchcode1103
dc.subject.fieldofresearchcode1114
dc.subject.keywordsBone marrow transplantation
dc.subject.keywordsScleroderma
dc.subject.keywordsBronchiolitis obliterans
dc.titleCorruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorCheong, Melody S.


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record