Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice.

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dc.contributor.author Sedger, LM
dc.contributor.author Katewa, A
dc.contributor.author Pettersen, AK
dc.contributor.author Osvath, SO
dc.contributor.author Farrell, G
dc.contributor.author Stewart, G
dc.contributor.author Bendall, LJ
dc.contributor.author Alexander, SI
dc.date.accessioned 2011-02-07T06:24:54Z
dc.date.issued 2010-01
dc.identifier.citation Blood, 2010, 115 (16), pp. 3258 - 3268
dc.identifier.issn 0006-4971
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/13809
dc.description.abstract To delineate the relative roles of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand in lymphocyte biology and lymphoproliferative disease, we generated mice defective in both molecules. B6.GT mice develop severe polyclonal lymphoproliferative disease because of accumulating CD3+CD4CD8B220+ T cells, CD4+ and CD8+ T cells, and follicular B cells, and mice die prematurely from extreme lymphocytosis, thrombocytopenia, and hemorrhage. Accumulating lymphocytes resembled antigen-experienced lymphocytes, consistent with the maximal resistance of B6.GT CD4+ and CD8+ T cell to activation-induced cell death. More specifically, we show that TRAIL contributes to Fas ligand-mediated activation-induced cell death and controls lymphocyte apoptosis in the presence of interferon-{gamma} once antigen stimulation is removed. Furthermore, dysregulated lymphocyte homeostasis results in the production of anti-DNA and rheumatoid factor autoantibodies, as well as antiplatelet IgM and IgG causing thrombocytopenia. Thus, B6.GT mice reveal new roles for TRAIL in lymphocyte homeostasis and autoimmune lymphoproliferative syndromes and are a model of spontaneous idiopathic thrombocytopenia purpura secondary to lymphoproliferative disease
dc.publisher American Society of Hematology
dc.relation.isbasedon 10.1182/blood-2009-11-255497
dc.title Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice.
dc.type Journal Article
dc.parent Blood
dc.journal.volume 16
dc.journal.volume 115
dc.journal.number 16 en_US
dc.publocation USA en_US
dc.identifier.startpage 3258 en_US
dc.identifier.endpage 3268 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 0601 Biochemistry and Cell Biology
dc.personcode 102397
dc.personcode 103839
dc.personcode 107692
dc.percentage 100 en_US
dc.classification.name Biochemistry and Cell Biology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords NA en_US
dc.description.keywords NA
dc.description.keywords NA
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science


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