Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-6
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10387937, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10601352, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10605044, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10706060, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10793165, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10852622, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10857849, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10866444, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10891472, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10919598, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-10979980, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-11110712, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-11313285, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-11483763, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-11792372, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-11884450, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-11986199, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-12001998, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-12091365, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-12163567, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-12424195, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-12426560, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-14523046, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-14550805, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-14563643, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-14769851, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15070675, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15249593, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15331748, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15855275, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15880112, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15897278, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-15956289, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-16037386, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-16105972, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-16291587, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-16498450, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-16920923, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-17213290, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-17395784, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-17438575, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-18011, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-18334670, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-18815289, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-19223585, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-19258596, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-2885638, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-2935484, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-3263049, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-6406592, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-6989042, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-7579369, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-7800006, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-7907102, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-8963063, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9037059, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9118285, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9255622, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9345067, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9834254, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9885208, http://linkedlifedata.com/resource/pubmed/commentcorrection/19955659-9950752
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1558-8238
pubmed:author
More...