{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:27:59Z","timestamp":1791052079553,"version":"4.1.0"},"reference-count":38,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,6,7]]},"abstract":"<jats:p>Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-\u03b3\u2013producing effector\u2013memory and proliferative memory T cells were compared in 79 vaccinees 13\u201325 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-\u03b3\u2013producing effector\u2013memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-\u03b3\u2013producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector\u2013memory T cells. Programmed revaccination boosted both IFN-\u03b3 and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector\u2013memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.<\/jats:p>","DOI":"10.1084\/jem.20032083","type":"journal-article","created":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T22:53:10Z","timestamp":1086648790000},"page":"1585-1593","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":115,"title":["Distinct Time Effects of Vaccination on Long-Term Proliferative and IFN-\u03b3\u2013producing T Cell Memory to Smallpox in Humans"],"prefix":"10.1084","volume":"199","author":[{"given":"Behazine","family":"Combadiere","sequence":"first","affiliation":[{"name":"1 Laboratoire d'Immunologie Cellulaire, INSERM U543,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Boissonnas","sequence":"additional","affiliation":[{"name":"1 Laboratoire d'Immunologie Cellulaire, INSERM U543,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guislaine","family":"Carcelain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Lefranc","sequence":"additional","affiliation":[{"name":"1 Laboratoire d'Immunologie Cellulaire, INSERM U543,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assia","family":"Samri","sequence":"additional","affiliation":[{"name":"1 Laboratoire d'Immunologie Cellulaire, INSERM U543,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327ois","family":"Bricaire","sequence":"additional","affiliation":[{"name":"2Service de Maladies Infectieuses, Ho\u0302pital Pitie\u0301-Salpe\u0301trie\u0300re, Universite\u0301 Pierre et Marie Curie, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Debre","sequence":"additional","affiliation":[{"name":"1 Laboratoire d'Immunologie Cellulaire, INSERM U543,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Autran","sequence":"additional","affiliation":[{"name":"1 Laboratoire d'Immunologie Cellulaire, INSERM U543,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,6,7]]},"reference":[{"key":"2023072512190833900_BIB1","first-page":"S53","volume":"17","year":"1999","journal-title":"Vaccine."},{"key":"2023072512190833900_BIB2"},{"key":"2023072512190833900_BIB3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nri778","volume":"2","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2023072512190833900_BIB4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S0952-7915(00)00211-9","volume":"13","year":"2001","journal-title":"Curr. Opin. Immunol."},{"key":"2023072512190833900_BIB5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1098\/rstb.2000.0576","volume":"355","year":"2000","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"2023072512190833900_BIB6","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1084\/jem.20001021","volume":"195","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072512190833900_BIB7","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/0952-7915(94)90139-2","volume":"6","year":"1994","journal-title":"Curr. Opin. Immunol."},{"key":"2023072512190833900_BIB8","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1084\/jem.176.5.1273","volume":"176","year":"1992","journal-title":"J. Exp. Med."},{"key":"2023072512190833900_BIB9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1084\/jem.188.1.71","volume":"188","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072512190833900_BIB10","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.4049\/jimmunol.166.3.1554","volume":"166","year":"2001","journal-title":"J. Immunol."},{"key":"2023072512190833900_BIB11","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/90950","volume":"7","year":"2001","journal-title":"Nat. Med."},{"key":"2023072512190833900_BIB12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev.immunol.16.1.201","volume":"16","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"2023072512190833900_BIB13","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev.immunol.20.100101.151926","volume":"20","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"2023072512190833900_BIB14","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/369652a0","volume":"369","year":"1994","journal-title":"Nature."},{"key":"2023072512190833900_BIB15","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4049\/jimmunol.169.1.90","volume":"169","year":"2002","journal-title":"J. Immunol."},{"key":"2023072512190833900_BIB16","first-page":"26","volume":"98","year":"2002","journal-title":"Nurs. Times."},{"key":"2023072512190833900_BIB17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1086\/323897","volume":"34","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"2023072512190833900_BIB18","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1126\/science.294.5544.985","volume":"294","year":"2001","journal-title":"Science."},{"key":"2023072512190833900_BIB19","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/infdis\/161.3.446","volume":"161","year":"1990","journal-title":"J. Infect. Dis."},{"key":"2023072512190833900_BIB20","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1128\/jvi.70.4.2627-2631.1996","volume":"70","year":"1996","journal-title":"J. Virol."},{"key":"2023072512190833900_BIB21","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nm917","volume":"9","year":"2003","journal-title":"Nat Med"},{"key":"2023072512190833900_BIB22","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/44385","volume":"401","year":"1999","journal-title":"Nature."},{"key":"2023072512190833900_BIB23","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1084\/jem.20022222","volume":"197","year":"2003","journal-title":"J. Exp. Med."},{"key":"2023072512190833900_BIB24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0022-1759(02)00328-9","volume":"272","year":"2003","journal-title":"J. Immunol. Methods."},{"key":"2023072512190833900_BIB25","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.4049\/jimmunol.171.7.3837","volume":"171","year":"2003","journal-title":"J. Immunol."},{"key":"2023072512190833900_BIB26","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1056\/NEJMoa013431","volume":"346","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"2023072512190833900_BIB27","first-page":"966","volume":"103","year":"2003","journal-title":"Blood"},{"key":"2023072512190833900_BIB28","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1084\/jem.20031598","volume":"198","year":"2003","journal-title":"J. Exp. Med."},{"key":"2023072512190833900_BIB29","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.4049\/jimmunol.161.9.4530","volume":"161","year":"1998","journal-title":"J. Immunol."},{"key":"2023072512190833900_BIB30","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1126\/science.286.5443.1377","volume":"286","year":"1999","journal-title":"Science."},{"key":"2023072512190833900_BIB31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1074-7613(00)80091-6","volume":"11","year":"1999","journal-title":"Immunity."},{"key":"2023072512190833900_BIB32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-4615-0757-4_15","volume":"512","year":"2002","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023072512190833900_BIB33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1600-065X.1997.tb01010.x","volume":"159","year":"1997","journal-title":"Immunol. Rev."},{"key":"2023072512190833900_BIB34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/76907","volume":"1","year":"2000","journal-title":"Nat. Immunol."},{"key":"2023072512190833900_BIB35","first-page":"225","volume":"4","year":"2003","journal-title":"Nat Immunol"},{"key":"2023072512190833900_BIB36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1001\/jama.290.1.23","volume":"290","year":"2003","journal-title":"JAMA."},{"key":"2023072512190833900_BIB37","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/nm0703-874","volume":"9","year":"2003","journal-title":"Nat. Med."},{"key":"2023072512190833900_BIB38","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1126\/science.277.5322.112","volume":"277","year":"1997","journal-title":"Science."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/199\/11\/1585\/1712386\/jem199111585.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/199\/11\/1585\/1712386\/jem199111585.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T12:29:37Z","timestamp":1690288177000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/199\/11\/1585\/39960\/Distinct-Time-Effects-of-Vaccination-on-Long-Term"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6,7]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2004,6,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20032083","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2004,6,7]]}}}