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dc.contributor.author Na, IK
dc.contributor.author Lu, SX
dc.contributor.author Yim, NL
dc.contributor.author Goldberg, GL
dc.contributor.author Tsai, J
dc.contributor.author Rao, U
dc.contributor.author Smith, OM
dc.contributor.author King, CG
dc.contributor.author Suh, D
dc.contributor.author Hirschhorn-Cymerman, D
dc.contributor.author Palomba, L
dc.contributor.author Penack, O
dc.contributor.author Holland, AM
dc.contributor.author Jenq, RR
dc.contributor.author Ghosh, A
dc.contributor.author Tran, H
dc.contributor.author Merghoub, T
dc.contributor.author Liu, C
dc.contributor.author Sempowski, GD
dc.contributor.author Ventevogel, M
dc.contributor.author Beauchemin, N
dc.contributor.author van den Brink, MR
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:27:54Z
dc.date.issued 2010-01
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/19955659
dc.identifier 39395
dc.identifier.citation J Clin Invest, 2010, 120 (1), pp. 343 - 356
dc.identifier.uri http://hdl.handle.net/10161/4323
dc.description.abstract Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.
dc.format.extent 343 - 356
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI39395
dc.subject Animals
dc.subject Bone Marrow Transplantation
dc.subject CASP8 and FADD-Like Apoptosis Regulating Protein
dc.subject Cell Movement
dc.subject Fas Ligand Protein
dc.subject Graft vs Host Disease
dc.subject Lymphocyte Activation
dc.subject Mice
dc.subject Mice, Inbred BALB C
dc.subject Mice, Inbred C57BL
dc.subject Receptors, OX40
dc.subject Receptors, TNF-Related Apoptosis-Inducing Ligand
dc.subject Stromal Cells
dc.subject T-Lymphocytes
dc.subject TNF-Related Apoptosis-Inducing Ligand
dc.subject Thymus Gland
dc.subject Transplantation, Homologous
dc.title The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-1-0 en_US
duke.description.endpage 356 en_US
duke.description.issue 1 en_US
duke.description.startpage 343 en_US
duke.description.volume 120 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/19955659
pubs.issue 1
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Duke Human Vaccine Institute
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published
pubs.volume 120
dc.identifier.eissn 1558-8238

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