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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1998-11-17
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pubmed:abstractText |
Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high viral burden can result in deletion of antigen-specific CTLs. We previously reported a potential mechanism for this deletion: tumor necrosis factor (TNF)-alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide-major histocompatibility complex. Here, we show that although death is mediated by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose dependence of TNF-alpha production nor that of TNF-RII expression can account for the dose dependence of apoptosis. Rather, a previously unrecognized effect of supraoptimal antigen in markedly decreasing levels of the antiapoptotic protein Bc1-2 was discovered and is likely to account for the gain in susceptibility or competence to sustain the death signal through TNF-RII. This decrease requires a signal through the TCR, not just through TNF-RII. Although death mediated by TNF-RII is not as widely studied as that mediated by TNF-RI, we show here that it is also dependent on proteolytic cleavage by caspases and triggered by a brief initial encounter with antigen. These results suggest that determinant density can regulate the immune response by altering the sensitivity of CTLs to the apoptotic effects of TNF-alpha by decreasing Bc1-2 levels.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9782116-1316930,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9782116-14224412,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/9782116-9584143
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1007
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
188
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1391-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9782116-Animals,
pubmed-meshheading:9782116-Antigens,
pubmed-meshheading:9782116-Apoptosis,
pubmed-meshheading:9782116-Caspases,
pubmed-meshheading:9782116-Major Histocompatibility Complex,
pubmed-meshheading:9782116-Mice,
pubmed-meshheading:9782116-Mice, Inbred BALB C,
pubmed-meshheading:9782116-Mice, Inbred DBA,
pubmed-meshheading:9782116-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:9782116-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:9782116-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:9782116-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
Supraoptimal peptide-major histocompatibility complex causes a decrease in bc1-2 levels and allows tumor necrosis factor alpha receptor II-mediated apoptosis of cytotoxic T lymphocytes.
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pubmed:affiliation |
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article
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