Source:http://linkedlifedata.com/resource/pubmed/id/15126416
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2004-5-20
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| pubmed:abstractText |
Graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation, leading to significant morbidity and mortality. Host-derived TNF-alpha play a role in the induction of allo-reactive donor T cell activation and the pathogenesis of GVHD. On the other hand, the precise role of donor-derived TNF-alpha in GVHD remains unclear. To elucidate this issue, we designed an acute GVHD model using (B6 x D2) F1 recipient mice transferred with spleen cells derived from either wild-type or TNF-alpha(-/-) C57BL/6 mice. Surprisingly, we found that spleen cells from TNF-alpha(-/-) mice induce more severe graft versus host reaction (GVHR) than wild-type spleen cells upon transfer into B6D2F1 mice. Transplantation of TNF-alpha(-/-) mouse spleen cells was associated with enhanced anti-host CTL generation and augmented deletion of host cells. Moreover, mice receiving TNF-alpha(-/-) cells showed significantly higher levels of serum IFN-gamma, which was mainly produced by donor CD8+ T cells. We also demonstrated that TNF-alpha deficiency in donor spleen cells caused a marked elevation of TNF-alpha producing capacity by LPS-stimulated host macrophages. Such enhanced GVHR was completely prevented by using TNF-alpha(-/-)IFN-gamma(-/-) splenic cells. Our findings demonstrate, for the first time, that donor-derived TNF-alpha suppress GVHR by inhibiting IFN-gamma-dependent donor type-1 immunity which is essential for host TNF-alpha elevation.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0953-8178
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| pubmed:author |
pubmed-author:ChamotoKenjiK,
pubmed-author:KoikeTakaoT,
pubmed-author:KosakaAkemiA,
pubmed-author:MatsuzakiJunkoJ,
pubmed-author:NishimuraTakashiT,
pubmed-author:SawadaKen-IchiK,
pubmed-author:SekikawaKenjiK,
pubmed-author:TakeshimaTsuguhideT,
pubmed-author:TogashiYujiY,
pubmed-author:TsujiTakemasaT,
pubmed-author:YamamotoSatoshiS,
pubmed-author:ZhangeYueY
|
| pubmed:copyrightInfo |
Copyright 2004 The Japanese Society for Immunology
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| pubmed:issnType |
Print
|
| pubmed:volume |
16
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
811-7
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| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:15126416-Animals,
pubmed-meshheading:15126416-B-Lymphocytes,
pubmed-meshheading:15126416-Cytotoxicity, Immunologic,
pubmed-meshheading:15126416-Disease Models, Animal,
pubmed-meshheading:15126416-Graft vs Host Disease,
pubmed-meshheading:15126416-Graft vs Host Reaction,
pubmed-meshheading:15126416-Interferon-gamma,
pubmed-meshheading:15126416-Lymphocyte Depletion,
pubmed-meshheading:15126416-Mice,
pubmed-meshheading:15126416-Mice, Inbred Strains,
pubmed-meshheading:15126416-Spleen,
pubmed-meshheading:15126416-Tissue Donors,
pubmed-meshheading:15126416-Tumor Necrosis Factor-alpha
|
| pubmed:year |
2004
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| pubmed:articleTitle |
Unexpected role of TNF-alpha in graft versus host reaction (GVHR): donor-derived TNF-alpha suppresses GVHR via inhibition of IFN-gamma-dependent donor type-1 immunity.
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| pubmed:affiliation |
Division of Immunoregulation, Institute for Genetic Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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