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rdf:type |
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lifeskim:mentions |
umls-concept:C0079904,
umls-concept:C0085358,
umls-concept:C0178539,
umls-concept:C0376315,
umls-concept:C0851285,
umls-concept:C1155065,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1413357,
umls-concept:C1706438,
umls-concept:C1879547,
umls-concept:C2698600
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pubmed:issue |
9
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pubmed:dateCreated |
2005-4-21
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pubmed:abstractText |
Cellular FLIP long form (c-FLIP(L)) was originally identified as an inhibitor of Fas (CD95/Apo-1). Subsequently, additional functions of c-FLIP(L) were identified through its association with receptor-interacting protein (RIP)1 and TNFR-associated factor 2 to activate NF-kappaB, as well as by its association with and activation of caspase-8. T cells from c-FLIP(L)-transgenic (Tg) mice manifest hyperproliferation upon activation, although it was not clear which of the various functions of c-FLIP(L) was involved. We have further explored the effect of c-FLIP(L) on CD8(+) effector T cell function and its mechanism of action. c-FLIP(L)-Tg CD8(+) T cells have increased proliferation and IL-2 responsiveness to cognate Ags as well as to low-affinity Ag variants, due to increased CD25 expression. They also have a T cytotoxic 2 cytokine phenotype. c-FLIP(L)-Tg CD8(+) T cells manifest greater caspase activity and NF-kappaB activity upon activation. Both augmented proliferation and CD25 expression are blocked by caspase inhibition. c-FLIP(L) itself is a substrate of the caspase activity in effector T cells, being cleaved to a p43(FLIP) form. p43(FLIP) more efficiently recruits RIP1 than full-length c-FLIP(L) to activate NF-kappaB. c-FLIP(L) and RIP1 also coimmunoprecipitate with active caspase-8 in effector CD8(+) T cells. Thus, one mechanism by which c-FLIP(L) influences effector T cell function is through its activation of caspase-8, which in turn cleaves c-FLIP(L) to allow RIP1 recruitment and NF-kappaB activation. This provides a partial explanation of why caspase activity is required to initiate proliferation of resting T cells.
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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/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cflar protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Egg Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/OVA-8,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RIPK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor-Interacting Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Ripk1 protein, mouse
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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 |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
174
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5270-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15843523-Animals,
pubmed-meshheading:15843523-Antigens,
pubmed-meshheading:15843523-Antigens, CD28,
pubmed-meshheading:15843523-Antigens, CD95,
pubmed-meshheading:15843523-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:15843523-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15843523-Caspase 8,
pubmed-meshheading:15843523-Caspases,
pubmed-meshheading:15843523-Cell Line,
pubmed-meshheading:15843523-Cells, Cultured,
pubmed-meshheading:15843523-Dose-Response Relationship, Immunologic,
pubmed-meshheading:15843523-Egg Proteins,
pubmed-meshheading:15843523-Female,
pubmed-meshheading:15843523-Humans,
pubmed-meshheading:15843523-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15843523-Lymphocyte Activation,
pubmed-meshheading:15843523-Male,
pubmed-meshheading:15843523-Mice,
pubmed-meshheading:15843523-Mice, Inbred C57BL,
pubmed-meshheading:15843523-Mice, Transgenic,
pubmed-meshheading:15843523-NF-kappa B,
pubmed-meshheading:15843523-Ovalbumin,
pubmed-meshheading:15843523-Peptide Fragments,
pubmed-meshheading:15843523-Proteins,
pubmed-meshheading:15843523-Receptor-Interacting Protein Serine-Threonine Kinases,
pubmed-meshheading:15843523-Receptors, Interleukin-2,
pubmed-meshheading:15843523-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Cellular FLIP (long form) regulates CD8+ T cell activation through caspase-8-dependent NF-kappa B activation.
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pubmed:affiliation |
Immunobiology Program, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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