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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
43
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pubmed:dateCreated |
2010-10-27
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pubmed:abstractText |
Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those that received allogeneic WT splenocytes. Donor CD8(+) T cells deficient in DNAM-1 showed significantly less proliferation and infiltration of the liver and intestines of recipient mice and produced less IFN-? after coculture with allogeneic splenocytes than WT CD8(+) T cells. Mice prophylactically treated with an anti-DNAM-1 antibody showed milder GVHD and lower mortality than those treated with a control antibody. Moreover, treatment with a single administration of the antibody after the overt onset of GVHD ameliorated GVHD and prolonged survival. Finally, we show that the anti-DNAM-1 antibody therapy also ameliorated the overt GVHD in lethally irradiated mice after MHC-matched, minor antigen-mismatched bone marrow transplantation. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18593-8
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pubmed:dateRevised |
2011-4-18
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pubmed:meshHeading |
pubmed-meshheading:20937876-Acute Disease,
pubmed-meshheading:20937876-Animals,
pubmed-meshheading:20937876-Antibodies, Monoclonal,
pubmed-meshheading:20937876-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:20937876-Bone Marrow Transplantation,
pubmed-meshheading:20937876-CD4-Positive T-Lymphocytes,
pubmed-meshheading:20937876-CD8-Positive T-Lymphocytes,
pubmed-meshheading:20937876-Cell Proliferation,
pubmed-meshheading:20937876-Female,
pubmed-meshheading:20937876-Graft vs Host Disease,
pubmed-meshheading:20937876-Interferon-gamma,
pubmed-meshheading:20937876-Ligands,
pubmed-meshheading:20937876-Male,
pubmed-meshheading:20937876-Mice,
pubmed-meshheading:20937876-Mice, Inbred BALB C,
pubmed-meshheading:20937876-Mice, Inbred C3H,
pubmed-meshheading:20937876-Mice, Inbred C57BL,
pubmed-meshheading:20937876-Mice, Knockout,
pubmed-meshheading:20937876-Transplantation, Homologous
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pubmed:year |
2010
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pubmed:articleTitle |
Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice.
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pubmed:affiliation |
Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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