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rdf:type |
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lifeskim:mentions |
umls-concept:C0013126,
umls-concept:C0014072,
umls-concept:C0033414,
umls-concept:C0039194,
umls-concept:C0178539,
umls-concept:C0597298,
umls-concept:C0678889,
umls-concept:C0871261,
umls-concept:C1413357,
umls-concept:C1514559,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
11
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pubmed:dateCreated |
2004-11-23
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pubmed:abstractText |
Cellular FLIP (c-FLIP) is an endogenous inhibitor of death receptor-induced apoptosis through the caspase 8 pathway. It is an NF-kappaB-inducible protein thought to promote the survival of T cells upon activation, and its down-regulation has been implicated in activation-induced cell death. We have generated transgenic mice overexpressing human c-FLIP long form (c-FLIP(L)) specifically in T cells using the CD2 promoter (TgFLIP(L)). TgFLIP(L) mice exhibit increased IgG1 production upon stimulation by a T cell-dependent Ag and a markedly enhanced contact hypersensitivity response to allergen. In addition to showing augmented Th2-type responses, TgFLIP(L) mice are resistant to the development of myelin oligodendrocyte glycoprotein 35-55 peptide-induced experimental autoimmune encephalomyelitis, a Th1-driven autoimmune disease. In vitro analyses revealed that T cells of TgFLIP(L) mice proliferate normally, but produce higher levels of IL-2 and show preferential maturation of Th2 cytokine-producing cells in response to antigenic stimulation. After adoptive transfer, these (Th2) cells protected wild-type recipient mice from experimental autoimmune encephalomyelitis induction. Our results show that the constitutive overexpression of c-FLIP(L) in T cells is sufficient to drive Th2 polarization of effector T cell responses and indicate that it might function as a key regulator of Th cell differentiation.
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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/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantibodies,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cflar protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/myelin oligodendrocyte...
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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 |
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pubmed:issnType |
Print
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pubmed:day |
1
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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 |
6619-26
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15557152-Adjuvants, Immunologic,
pubmed-meshheading:15557152-Adoptive Transfer,
pubmed-meshheading:15557152-Animals,
pubmed-meshheading:15557152-Antibodies, Monoclonal,
pubmed-meshheading:15557152-Antigens, CD3,
pubmed-meshheading:15557152-Antigens, CD95,
pubmed-meshheading:15557152-Autoantibodies,
pubmed-meshheading:15557152-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:15557152-Cell Death,
pubmed-meshheading:15557152-Cell Differentiation,
pubmed-meshheading:15557152-Dermatitis, Contact,
pubmed-meshheading:15557152-Encephalomyelitis, Autoimmune, Experimental,
pubmed-meshheading:15557152-Glycoproteins,
pubmed-meshheading:15557152-Humans,
pubmed-meshheading:15557152-Immunity, Innate,
pubmed-meshheading:15557152-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15557152-Lymphocyte Activation,
pubmed-meshheading:15557152-Mice,
pubmed-meshheading:15557152-Mice, Inbred C57BL,
pubmed-meshheading:15557152-Mice, Inbred CBA,
pubmed-meshheading:15557152-Mice, Transgenic,
pubmed-meshheading:15557152-Peptide Fragments,
pubmed-meshheading:15557152-Protein Isoforms,
pubmed-meshheading:15557152-T-Lymphocyte Subsets,
pubmed-meshheading:15557152-Th2 Cells
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pubmed:year |
2004
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pubmed:articleTitle |
Cellular FLIP (long isoform) overexpression in T cells drives Th2 effector responses and promotes immunoregulation in experimental autoimmune encephalomyelitis.
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pubmed:affiliation |
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, National Center for Scientific Research Demokritos, Athens, Greece.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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