Rapid Induction of Apoptosis in CD8+ HIV-1 Envelope-Specific Murine CTLs by Short Exposure to Antigenic Peptide
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- Megumi Takahashi
- Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,
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- Eiichi Osono
- Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,
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- Yohko Nakagawa
- Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,
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- Jian Wang
- Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892
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- Jay A Berzofsky
- Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892
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- David H Margulies
- Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892
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- Hidemi Takahashi
- Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,
書誌事項
- 公開日
- 2002-12-01
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.169.11.6588
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>During primary viral infection, in vivo exposure to high doses of virus causes a loss of Ag-specific CD8+ T cells. This phenomenon, termed clonal exhaustion, and other mechanisms by which CTLs are deleted are poorly understood. Here we show evidence for a novel form of cell death in which recently stimulated CD8+ HIV-1 envelope gp160-specific murine CTLs become apoptotic in vitro after brief exposure to free antigenic peptide (P18-I10). Peak apoptosis occurred within 3 h of treatment with peptide, and the level of apoptosis was dependent on both the time after initial stimulation with target cells and the number of targets. Using T cell-specific H-2Dd/P18-I10 tetramers, we observed that the apoptosis was induced by such complexes. Induction of apoptosis was blocked by cyclosporin A, a caspase 3 inhibitor, and a mitogen-activated protein kinase inhibitor, but not by Abs to either Fas ligand or to TNF-α. Thus, these observations suggest the existence of a Fas- or TNF-α-independent pathway initiated by TCR signaling that is involved in the rapid induction of CTL apoptosis. Such a pathway may prove important in the mechanism by which virus-specific CTLs are deleted in the presence of high viral burdens.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 169 (11), 6588-6593, 2002-12-01
Oxford University Press (OUP)