Source:http://linkedlifedata.com/resource/pubmed/id/10799894
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2000-6-7
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| pubmed:abstractText |
CTLA-4-mediated inhibition of T cell activation may be accomplished by competition for ligands and/or by signals mediated through the intracellular domain. Studies have implicated Tyr201 in the cytoplasmic domain of CTLA-4 in regulating CTLA-4 signal transduction and intracellular trafficking. To investigate the mechanism of CTLA-4 function in vivo, transgenes encoding wild-type CTLA-4 (FL), a mutant lacking the cytoplasmic domain of CTLA-4 (DeltaCTLA-4 tail), or a CTLA-4 Tyr201 mutant (Y201V) were introduced into CTLA-4-deficient mice. CTLA-4-/- mice display an autoimmune lymphoproliferative disorder resulting in tissue destruction and early death. When either the FL or the Y201V transgene was bred into CTLA-4-/- animals, a complete rescue from lymphoproliferation and autoimmunity was observed. In contrast, CTLA-4-/- mice expressing the DeltaCTLA-4 tail transgene were long lived with no evidence of multiorgan lymphocytic infiltration, but exhibited lymphadenopathy and accumulated large numbers of activated T cells. Furthermore, these animals displayed a Th2-biased phenotype which conferred susceptibility to Leishmania infection. These results indicate that the inhibitory effect of CTLA-4 is mediated in part through the ability of the extracellular domain to compete for ligands. The cytoplasmic domain of CTLA-4, however, is required for complete inhibitory function of the receptor and for regulation of Th cell differentiation in vivo.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
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/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
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| pubmed:volume |
164
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5319-27
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10799894-Amino Acid Sequence,
pubmed-meshheading:10799894-Animals,
pubmed-meshheading:10799894-Antigens, CD,
pubmed-meshheading:10799894-Antigens, Differentiation,
pubmed-meshheading:10799894-CTLA-4 Antigen,
pubmed-meshheading:10799894-Crosses, Genetic,
pubmed-meshheading:10799894-Genes, Lethal,
pubmed-meshheading:10799894-Genetic Predisposition to Disease,
pubmed-meshheading:10799894-Homeostasis,
pubmed-meshheading:10799894-Immunoconjugates,
pubmed-meshheading:10799894-Immunophenotyping,
pubmed-meshheading:10799894-Leishmania major,
pubmed-meshheading:10799894-Leishmaniasis, Cutaneous,
pubmed-meshheading:10799894-Lymphatic Diseases,
pubmed-meshheading:10799894-Lymphocyte Activation,
pubmed-meshheading:10799894-Mice,
pubmed-meshheading:10799894-Mice, Inbred BALB C,
pubmed-meshheading:10799894-Mice, Inbred C57BL,
pubmed-meshheading:10799894-Mice, Knockout,
pubmed-meshheading:10799894-Mice, Transgenic,
pubmed-meshheading:10799894-Molecular Sequence Data,
pubmed-meshheading:10799894-Splenomegaly,
pubmed-meshheading:10799894-T-Lymphocytes,
pubmed-meshheading:10799894-Th2 Cells,
pubmed-meshheading:10799894-Transgenes
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| pubmed:year |
2000
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| pubmed:articleTitle |
Structural analysis of CTLA-4 function in vivo.
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| pubmed:affiliation |
Gwen Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA. emastell@delphi.bsd.uchicago.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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