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rdf:type |
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lifeskim:mentions |
umls-concept:C0009528,
umls-concept:C0085358,
umls-concept:C0205276,
umls-concept:C0225336,
umls-concept:C0332298,
umls-concept:C0871261,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1515895,
umls-concept:C1704632,
umls-concept:C1706438,
umls-concept:C1706817,
umls-concept:C2698600,
umls-concept:C2911692
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pubmed:issue |
8
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pubmed:dateCreated |
2009-8-7
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pubmed:abstractText |
CD8 T cells primed by transplantation recognize allogeneic class I MHC molecules expressed on graft vascular endothelium and contribute to allograft injury. We previously showed that immune cell-derived complement activation fragments are integral to T cell activation/expansion. Herein we tested the impact of local complement production/activation on T cell/endothelial cell (EC) interactions. We found that proinflammatory cytokines upregulated alternative pathway complement production by ECs, yielding C5a. We further found that ECs deficient in the cell surface C3/C5 convertase regulator decay accelerating factor (DAF, CD55) induced greater CD8 T-cell proliferation and more IFNgamma(+) and perforin(+) effector cells than wild-type (WT) ECs. Allogeneic C3(-/-) EC induced little or no CD8 responses. Abrogation of responses following C5a receptor (C5aR) blockade, or augmentation following addition of recombinant C5a demonstrated that the effects were mediated through T-cell-expressed-C5aR interactions. Analyses of in vivo CD8 cell responses to transplanted heart grafts deficient in EC DAF showed similar augmentation. The findings reveal that EC-derived complement triggers secondary CD8 T-cell differentiation and expansion and argue that targeting complement and/or C5aR could limit T-cell-mediated graft injury.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD55,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C3,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C3-C5 Convertases,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C5a,
http://linkedlifedata.com/resource/pubmed/chemical/Complement System Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Anaphylatoxin C5a,
http://linkedlifedata.com/resource/pubmed/chemical/decay-accelerating factor 1, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1600-6143
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1784-95
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pubmed:meshHeading |
pubmed-meshheading:19563342-Animals,
pubmed-meshheading:19563342-Antigens, CD55,
pubmed-meshheading:19563342-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19563342-Cell Communication,
pubmed-meshheading:19563342-Cell Differentiation,
pubmed-meshheading:19563342-Cell Proliferation,
pubmed-meshheading:19563342-Cells, Cultured,
pubmed-meshheading:19563342-Complement C3,
pubmed-meshheading:19563342-Complement C3-C5 Convertases,
pubmed-meshheading:19563342-Complement C5a,
pubmed-meshheading:19563342-Complement System Proteins,
pubmed-meshheading:19563342-Cytokines,
pubmed-meshheading:19563342-Endothelium, Vascular,
pubmed-meshheading:19563342-Female,
pubmed-meshheading:19563342-Male,
pubmed-meshheading:19563342-Mice,
pubmed-meshheading:19563342-Mice, Inbred BALB C,
pubmed-meshheading:19563342-Mice, Inbred C57BL,
pubmed-meshheading:19563342-Mice, Knockout,
pubmed-meshheading:19563342-Mice, Transgenic,
pubmed-meshheading:19563342-Models, Animal,
pubmed-meshheading:19563342-Receptor, Anaphylatoxin C5a
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pubmed:year |
2009
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pubmed:articleTitle |
Primed CD8(+) T-cell responses to allogeneic endothelial cells are controlled by local complement activation.
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pubmed:affiliation |
Department of Medicine, Recanati Transplant Institute, Mount Sinai School of Medicine, New York, NY, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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