Document Detail

Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice.
MedLine Citation:
PMID:  20937876     Owner:  NLM     Status:  MEDLINE    
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-γ 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.
Tsukasa Nabekura; Kazuko Shibuya; Eri Takenaka; Hirayasu Kai; Kai Shibata; Yumi Yamashita; Kyoichi Harada; Satoko Tahara-Hanaoka; Shin-ichiro Honda; Akira Shibuya
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-11
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-27     Completed Date:  2010-11-22     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18593-8     Citation Subset:  IM    
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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MeSH Terms
Acute Disease
Antibodies, Monoclonal / therapeutic use
Antigens, Differentiation, T-Lymphocyte / genetics,  immunology*
Bone Marrow Transplantation / adverse effects,  immunology,  pathology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology,  pathology
Cell Proliferation
Graft vs Host Disease / etiology*,  immunology*,  pathology,  therapy
Interferon-gamma / biosynthesis
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Transplantation, Homologous
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, Differentiation, T-Lymphocyte; 0/CD226 antigen; 0/Ligands; 82115-62-6/Interferon-gamma
Comment In:
Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):E32-3; author reply E34   [PMID:  21321238 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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