Source:http://linkedlifedata.com/resource/pubmed/id/17508005
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2007-6-20
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pubmed:abstractText |
We studied the effect of CTLA-4 blockade on graft-versus-leukemia and graft-versus-host responses in a mouse model of minor histocompatibility-mismatched bone marrow transplantation. Early CTLA-4 blockade induced acute graft-versus-host disease. Delayed CTLA-4 blockade resulted in a lethal condition with lymphosplenomegaly, but with stable mixed T-cell chimerism, unchanged alloreactive T-cell frequencies and absent anti-host reactivity in vitro. In contrast, multiorgan lymphoproliferative disease with autoimmune hepatitis and circulating anti-DNA auto-antibodies were documented. Splenic lymphocytes exhibited ex vivo spontaneous proliferation and a marked proliferative response against host-type dendritic cells pulsed with syngeneic (host-type) tissue-peptides. Both phenomena were exclusively mediated by host and not donor T cells, supporting an autoimmune pathogenesis. Selectively host-derived T-cell immune reactivity was equally documented against leukemia-peptide-pulsed dendritic cells, and this was paralleled by a strong in vivo antileukemic effect in anti-CTLA-4-treated and subsequently leukemia-challenged chimeras. In conclusion, delayed CTLA-4 blockade induced a host-derived antileukemic effect, occurring in the context of an autoimmune syndrome and strictly separated from graft-versus-host disease. Both antileukemic and autoimmune responses depended on the allogeneic component, as neither effect was seen after syngeneic bone marrow transplantation. Our findings reveal the potential of using CTLA-4 blockade to establish antileukemic effects after allogeneic hematopoietic stem cell transplantation, provided autoimmunity can be controlled.
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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 |
Jul
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pubmed:issn |
0887-6924
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pubmed:author |
pubmed-author:BilliauA DAD,
pubmed-author:BoolJJ,
pubmed-author:De Wolf-PeetersCC,
pubmed-author:FeverySS,
pubmed-author:GoebelsJJ,
pubmed-author:KasranAA,
pubmed-author:LanduytWW,
pubmed-author:LenaertsCC,
pubmed-author:RutgeertsOO,
pubmed-author:SagaertXX,
pubmed-author:SprangersBB,
pubmed-author:VandenberghePP,
pubmed-author:WaerMM
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pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1451-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17508005-Animals,
pubmed-meshheading:17508005-Antigens, CD,
pubmed-meshheading:17508005-Antigens, Differentiation,
pubmed-meshheading:17508005-Autoimmunity,
pubmed-meshheading:17508005-Bone Marrow Transplantation,
pubmed-meshheading:17508005-CTLA-4 Antigen,
pubmed-meshheading:17508005-Graft vs Host Disease,
pubmed-meshheading:17508005-Graft vs Leukemia Effect,
pubmed-meshheading:17508005-Histocompatibility,
pubmed-meshheading:17508005-Leukemia,
pubmed-meshheading:17508005-Mice,
pubmed-meshheading:17508005-T-Lymphocytes,
pubmed-meshheading:17508005-Transplantation Chimera,
pubmed-meshheading:17508005-Treatment Outcome
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pubmed:year |
2007
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pubmed:articleTitle |
CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease.
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pubmed:affiliation |
Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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