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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2004-12-8
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pubmed:abstractText |
Cbl-b negatively regulates CD28-dependent T cell activation. In this report, we tested the hypothesis that CD28 and CTLA-4 have opposite roles in tuning T cell activation threshold by controlling the levels of Cbl-b protein expression. We demonstrate that CD28 costimulation potentiates TCR-induced Cbl-b degradation, whereas CTLA-4-B7 interaction is required for Cbl-b re-expression. In support of this finding, Cbl-b expression in CTLA-4 knockout (KO) T cells is significantly reduced, and treating CTLA-4KO mice with human CTLA-4Ig to block CD28-B7 interaction restores Cbl-b expression on T cells. Furthermore, CD28 and CTLA-4 costimulatory effects are compromised in Cbl-bKO T cells. These observations indicate that CD28 and CTLA-4 tightly regulate Cbl-b expression which is critical for establishing the threshold for T cell activation.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
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, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cblb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:AdarichevVyacheslavaV,
pubmed-author:AlegreMaria-LuisaML,
pubmed-author:ChenLiepingL,
pubmed-author:ChongAnita S FAS,
pubmed-author:FinneganAlisonA,
pubmed-author:GálIstvánI,
pubmed-author:GlantTibor TTT,
pubmed-author:KorenyTamasT,
pubmed-author:LiDongdongD,
pubmed-author:MikeczKatalinK,
pubmed-author:ShaoQingQ,
pubmed-author:VermesCsabaC,
pubmed-author:XuXuemeiX,
pubmed-author:ZhangJianJ
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7135-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15585834-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:15585834-Adjuvants, Immunologic,
pubmed-meshheading:15585834-Animals,
pubmed-meshheading:15585834-Antigens, CD,
pubmed-meshheading:15585834-Antigens, CD28,
pubmed-meshheading:15585834-Antigens, CD80,
pubmed-meshheading:15585834-Antigens, Differentiation,
pubmed-meshheading:15585834-CTLA-4 Antigen,
pubmed-meshheading:15585834-Cell Proliferation,
pubmed-meshheading:15585834-Cells, Cultured,
pubmed-meshheading:15585834-Drug Synergism,
pubmed-meshheading:15585834-Female,
pubmed-meshheading:15585834-Growth Inhibitors,
pubmed-meshheading:15585834-Humans,
pubmed-meshheading:15585834-Immunoconjugates,
pubmed-meshheading:15585834-Lymphocyte Activation,
pubmed-meshheading:15585834-Mice,
pubmed-meshheading:15585834-Mice, Inbred BALB C,
pubmed-meshheading:15585834-Mice, Inbred C57BL,
pubmed-meshheading:15585834-Mice, Knockout,
pubmed-meshheading:15585834-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:15585834-T-Lymphocyte Subsets,
pubmed-meshheading:15585834-Ubiquitin-Protein Ligases
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pubmed:year |
2004
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pubmed:articleTitle |
Cutting edge: Cbl-b: one of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation.
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pubmed:affiliation |
Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, 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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