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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-11-7
pubmed:abstractText
We studied the role of CD28 in T-cell biology and T cell-mediated pathology using a novel mouse anti-mouse CD28 antibody, E18, which recognizes an epitope close to the B7 binding site. In vitro, this antibody completely blocked binding of B7 molecules to CD28 expressed on mouse thymocytes but enhanced anti-CD3-induced proliferation of peripheral T cells. Injections of E18 monoclonal antibody into normal BALB/c mice in vivo, however, led to a reversible reduction in Treg cell frequencies among CD4(+) cells, both in the thymus and in secondary lymphoid organs, suggesting that E18 acted as an inhibitor of CD28 signaling under these conditions. Antagonistic activity of E18 in vivo was further implied by suppressed responses of conventional CD4(+) T cells to stimulation with the superantigen staphylococcal enterotoxin B and in a model of acute graft-versus-host disease. In contrast to healthy mice, intact monoclonal antibody E18, but not its nonstimulatory Fab fragment, increased the frequencies of Treg cells among CD4(+) T cells in these pro-inflammatory settings allowing for efficacious protection from acute graft-versus-host disease. Thus, the agonistic signal generated by conventional, ie, nonsuperagonistic, anti-CD28 antibodies is important for their immunotherapeutic potential in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4328-36
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18780833-Animals, pubmed-meshheading:18780833-Antibodies, Monoclonal, pubmed-meshheading:18780833-Antigens, CD28, pubmed-meshheading:18780833-Antigens, CD3, pubmed-meshheading:18780833-Antigens, CD80, pubmed-meshheading:18780833-Binding Sites, Antibody, pubmed-meshheading:18780833-Bone Marrow Transplantation, pubmed-meshheading:18780833-Disease Models, Animal, pubmed-meshheading:18780833-Enterotoxins, pubmed-meshheading:18780833-Graft vs Host Disease, pubmed-meshheading:18780833-Immunoglobulin Fab Fragments, pubmed-meshheading:18780833-Mice, pubmed-meshheading:18780833-Mice, Inbred BALB C, pubmed-meshheading:18780833-Protein Binding, pubmed-meshheading:18780833-Signal Transduction, pubmed-meshheading:18780833-T-Lymphocytes, Regulatory, pubmed-meshheading:18780833-Thymus Gland, pubmed-meshheading:18780833-Transplantation, Homologous
pubmed:year
2008
pubmed:articleTitle
Protection from graft-versus-host disease with a novel B7 binding site-specific mouse anti-mouse CD28 monoclonal antibody.
pubmed:affiliation
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany. niklas.beyersdorf@vim.uni-wuerzburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't