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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1998-8-14
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pubmed:abstractText |
Ligation of cytotoxic T lymphocyte antigen 4 (CTLA4) appears to inhibit T cell responses. Four mechanisms have been proposed to explain the inhibitory activity of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of signaling molecules away from CD28 via endocytosis; delivery of a signal that antagonizes a CD28 signal; and delivery of a signal that antagonizes a T cell receptor (TCR) signal. As three of these potential mechanisms involve functional antagonism of CD28, an experimental model was designed to determine whether CTLA4 could inhibit T cell function in the absence of CD28. TCR transgenic/recombinase activating gene 2-deficient/CD28-wild-type or CD28-deficient mice were generated and immunized with an antigen-expressing tumor. Primed T cells from both types of mice produced cytokines and proliferated in response to stimulator cells lacking B7 expression. However, whereas the response of CD28+/+ T cells was augmented by costimulation with B7-1, the response of the CD28-/- T cells was strongly inhibited. This inhibition was reversed by monoclonal antibody against B7-1 or CTLA4. Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-1313950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-1714933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-3261843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7481803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7534617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7534620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7543139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7584144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7621080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7678111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7688139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7807015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-7882171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8294862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8596936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8609411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8610339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8638161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8666770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8676074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8676075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8717514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-8943377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-9036940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-9133420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-9200449,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-9354465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-9362525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9653097-9366389
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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, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD80,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Rag2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/V(D)J recombination activating...,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1007
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
188
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
205-10
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9653097-Animals,
pubmed-meshheading:9653097-Antigens, CD,
pubmed-meshheading:9653097-Antigens, CD28,
pubmed-meshheading:9653097-Antigens, CD80,
pubmed-meshheading:9653097-Antigens, Differentiation,
pubmed-meshheading:9653097-CTLA-4 Antigen,
pubmed-meshheading:9653097-Cell Division,
pubmed-meshheading:9653097-Cell Line,
pubmed-meshheading:9653097-Cytokines,
pubmed-meshheading:9653097-DNA-Binding Proteins,
pubmed-meshheading:9653097-Immunoconjugates,
pubmed-meshheading:9653097-Mice,
pubmed-meshheading:9653097-Mice, Transgenic,
pubmed-meshheading:9653097-Receptors, Antigen, T-Cell,
pubmed-meshheading:9653097-Signal Transduction,
pubmed-meshheading:9653097-T-Lymphocytes
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pubmed:year |
1998
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pubmed:articleTitle |
B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28.
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pubmed:affiliation |
Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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