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rdf:type |
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lifeskim:mentions |
umls-concept:C0013081,
umls-concept:C0017262,
umls-concept:C0035820,
umls-concept:C0039194,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0205307,
umls-concept:C0288331,
umls-concept:C0337026,
umls-concept:C0385242,
umls-concept:C0445450,
umls-concept:C0597298,
umls-concept:C1332397,
umls-concept:C1413357,
umls-concept:C1522480,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2005-3-28
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pubmed:abstractText |
A systematic study was undertaken to characterize the role of APO 2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (APO2L/TRAIL) and Fas ligand (FasL) together with the expression of several anti- or proapoptotic proteins in the down-regulation of normal human T cell responses. We have observed for the first time that the higher sensitivity of normal human T cell blasts to apoptosis and activation-induced cell death (AICD) as compared with naive T cells correlates with the increased expression of Bcl-x short (Bcl-xS) and Bim. T cell blasts die in the absence of interleukin 2 (IL-2) with no additional effect of death receptor ligation. In the presence of IL-2, recombinant APO2L/TRAIL or cytotoxic anti-Fas monoclonal antibodies induce rather inhibition of IL-2-dependent growth and not cell death on normal human T cell blasts. This observation is of physiological relevance, as supernatants from T cell blasts, pulse-stimulated with phytohemagglutinin (PHA) or through CD3 or CD59 ligation and containing bioactive APO2L/TRAIL and/or FasL expressed on microvesicles or direct CD3 or CD59 ligation, had the same effect. Cell death was only observed in the presence of cycloheximide or after a pulse through CD3 or CD59, correlating with a net reduction in cellular Fas-associated death domain-like IL-1beta-converting enzyme-inhibitory protein long (c-FLIPL) and c-FLIPS expression. We also show that death receptor and free radical generation contribute, at least partially, to AICD induced by PHA and also to the inhibition of IL-2-dependent cell growth by CD3 or CD59 ligation. Finally, we have also shown that T cell blasts surviving PHA-induced AICD are memory CD44high cells with increased c-FLIPS and Bcl-xL expression.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl-2-like protein 11,
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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0741-5400
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
77
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
568-78
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pubmed:dateRevised |
2007-9-28
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pubmed:meshHeading |
pubmed-meshheading:15653751-Antigens, CD,
pubmed-meshheading:15653751-Apoptosis,
pubmed-meshheading:15653751-Apoptosis Regulatory Proteins,
pubmed-meshheading:15653751-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:15653751-Carrier Proteins,
pubmed-meshheading:15653751-Cell Death,
pubmed-meshheading:15653751-Fas Ligand Protein,
pubmed-meshheading:15653751-Gene Expression Regulation,
pubmed-meshheading:15653751-Humans,
pubmed-meshheading:15653751-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15653751-Lymphocyte Activation,
pubmed-meshheading:15653751-Membrane Glycoproteins,
pubmed-meshheading:15653751-Membrane Proteins,
pubmed-meshheading:15653751-Proto-Oncogene Proteins,
pubmed-meshheading:15653751-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15653751-T-Lymphocytes,
pubmed-meshheading:15653751-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:15653751-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15653751-bcl-X Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Down-regulation of normal human T cell blast activation: roles of APO2L/TRAIL, FasL, and c- FLIP, Bim, or Bcl-x isoform expression.
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pubmed:affiliation |
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, E-50009, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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