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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2008-12-17
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pubmed:abstractText |
CTLA-4 (CD152) negatively regulates T cell activation signaling, and the cytoplasmic domain of CTLA-4 (ctCTLA-4) itself has the capacity to inhibit T cell activation in vitro and in vivo. In this study, the inhibitory mechanisms of the cell-permeable recombinant protein Hph-1-ctCTLA-4 on T cell activation and its ability to prevent collagen-induced arthritis were analyzed. Hph-1-ctCTLA-4 prevented human and mouse T cell activation and proliferation by inhibition of T cell receptor-proximal signaling and the arrest of the cell cycle. Furthermore, Hph-1-ctCTLA-4 protected human umbilical vein endothelial cells (HUVEC) from the human CTL allo-response. The incidence and severity of collagen-induced arthritis were significantly reduced and the erosion of cartilage and bone was effectively prevented by i.v. injection and transdermal administration of Hph-1-ctCTLA-4. Inflammatory cytokine production (IL-1beta, IL-6, TNF-alpha, IL-17A) and collagen-specific antibody levels were significantly reduced, and the numbers of activated T cells and infiltrating granulocytes were substantially decreased. These results demonstrate that systemic or transdermal application of a cell-permeable form of the cytoplasmic domain of CTLA-4 offers an effective therapeutic approach for autoimmune diseases such as rheumatoid arthritis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-10477521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-10493833,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-10694513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-10799894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-10903737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-11062537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-11244036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-11244047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-11449357,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-11807776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-12359827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-12483717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-12724780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-14770176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-15039384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-15142525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-15322161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-15641090,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-15769927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-15972645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16007096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16163381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16293346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16405652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16551244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16604087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16724806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-16920972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-17020493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-8078923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-8290579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-8616886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-8717520,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-9008163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-9354465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-9846587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-9856951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19066215-9870876
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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/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/PHC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19875-80
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19066215-Animals,
pubmed-meshheading:19066215-Antigens, CD,
pubmed-meshheading:19066215-Arthritis, Experimental,
pubmed-meshheading:19066215-CTLA-4 Antigen,
pubmed-meshheading:19066215-Carrier Proteins,
pubmed-meshheading:19066215-Cartilage, Articular,
pubmed-meshheading:19066215-Cytoplasm,
pubmed-meshheading:19066215-Disease Models, Animal,
pubmed-meshheading:19066215-Humans,
pubmed-meshheading:19066215-Joints,
pubmed-meshheading:19066215-Lymphocyte Activation,
pubmed-meshheading:19066215-Mice,
pubmed-meshheading:19066215-Receptors, Antigen, T-Cell,
pubmed-meshheading:19066215-Recombinant Proteins,
pubmed-meshheading:19066215-T-Lymphocytes,
pubmed-meshheading:19066215-Transduction, Genetic
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pubmed:year |
2008
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pubmed:articleTitle |
Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis.
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pubmed:affiliation |
Department of Immunobiology, Yale University, School of Medicine, New Haven, CT 06520, USA.
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