{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T03:20:42Z","timestamp":1770088842583,"version":"3.49.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2002,12,1]],"date-time":"2002-12-01T00:00:00Z","timestamp":1038700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <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-\u03b1. Thus, these observations suggest the existence of a Fas- or TNF-\u03b1-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>","DOI":"10.4049\/jimmunol.169.11.6588","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:41:24Z","timestamp":1398022884000},"page":"6588-6593","source":"Crossref","is-referenced-by-count":18,"title":["Rapid Induction of Apoptosis in CD8+ HIV-1 Envelope-Specific Murine CTLs by Short Exposure to Antigenic Peptide"],"prefix":"10.1093","volume":"169","author":[{"given":"Megumi","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Osono","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohko","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A","family":"Berzofsky","sequence":"additional","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H","family":"Margulies","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidemi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,12,1]]},"reference":[{"key":"2026020209194001400_R1","first-page":"1383","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209194001400_R2","first-page":"2205","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209194001400_R3","first-page":"758","volume-title":"Nature","year":"1993"},{"key":"2026020209194001400_R4","first-page":"249","volume-title":"J. Exp. Med.","year":"1993"},{"key":"2026020209194001400_R5"},{"key":"2026020209194001400_R6","first-page":"9848","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020209194001400_R7","first-page":"485","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026020209194001400_R8","first-page":"1391","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020209194001400_R9","first-page":"348","volume-title":"Nature","year":"1995"},{"key":"2026020209194001400_R10","first-page":"3055","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2026020209194001400_R11","first-page":"1817","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020209194001400_R12","first-page":"3131","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020209194001400_R13","first-page":"1973","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020209194001400_R14","first-page":"333","volume-title":"Science","year":"1992"},{"key":"2026020209194001400_R15","first-page":"535","volume-title":"Nature","year":"1986"},{"key":"2026020209194001400_R16","first-page":"3105","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1988"},{"key":"2026020209194001400_R17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/oso\/9780199635696.003.0007","volume-title":"Cell Growth and Apoptosis: A Practical Approach","year":"1995"},{"key":"2026020209194001400_R18","first-page":"3860","volume-title":"Blood","year":"2001"},{"key":"2026020209194001400_R19","first-page":"118","volume-title":"Science","year":"1989"},{"key":"2026020209194001400_R20","first-page":"2023","volume-title":"J. Exp. Med.","year":"1989"},{"key":"2026020209194001400_R21","first-page":"199","volume-title":"Immunity","year":"1998"},{"key":"2026020209194001400_R22","first-page":"179","volume-title":"J. Mol. Biol.","year":"1998"},{"key":"2026020209194001400_R23","first-page":"591","volume-title":"Immunity","year":"2001"},{"key":"2026020209194001400_R24","first-page":"728","volume-title":"Nature","year":"1997"},{"key":"2026020209194001400_R25","first-page":"340","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026020209194001400_R26","first-page":"12378","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2026020209194001400_R27","first-page":"30417","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2026020209194001400_R28","first-page":"1017","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026020209194001400_R29","first-page":"26","volume-title":"Immunology","year":"1999"},{"key":"2026020209194001400_R30","first-page":"879","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026020209194001400_R31","first-page":"43","volume-title":"Int. Immunol.","year":"2001"},{"key":"2026020209194001400_R32","first-page":"2951","volume-title":"Eur. J. Immunol.","year":"2001"},{"key":"2026020209194001400_R33","first-page":"1601","volume-title":"Int. Immunol.","year":"1997"},{"key":"2026020209194001400_R34","first-page":"577","volume-title":"Eur. J. Immunol.","year":"1997"},{"key":"2026020209194001400_R35","first-page":"991","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026020209194001400_R36","first-page":"7515","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020209194001400_R37","first-page":"225","volume-title":"J. Hepatol.","year":"1996"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/169\/11\/6588\/62560631\/6588.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/169\/11\/6588\/62560631\/6588.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:27:31Z","timestamp":1770042451000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/169\/11\/6588\/8027192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,12,1]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2002,12,1]]},"published-print":{"date-parts":[[2002,12,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.169.11.6588","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2002,12]]},"published":{"date-parts":[[2002,12,1]]}}}