{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:32:50Z","timestamp":1770096770192,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"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":[[2005,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammatory cytokines such as IFN-\u03b3 and TNF produced by Ag-stimulated CD4+ and CD8+ T cells are important in defense against microbial infection. However, production of these cytokines must be tightly regulated to prevent immunopathology. Previous studies, conducted with BALB\/c mice, have suggested that 1) CD8+ T cells maintain IFN-\u03b3 production but transiently produce TNF in the continued presence of Ag and 2) lymphocytic choriomeningitis virus-specific and in vitro-propagated effector CD8+ T cells could rapidly cycle IFN-\u03b3 production ON\/OFF\/ON in response to Ag exposure, removal, and re-exposure. In contrast with CD8+ T cells, our results show that Listeria monocytogenes-specific CD4+ T cells from C57BL\/6 mice rapidly initiate (ON cycling) and maintain production of both IFN-\u03b3 and TNF in the continued presence of Ag. Upon Ag removal, production of both cytokines rapidly ceases (OFF cycling). However, if the initial stimulation was maximal, Ag-specific CD4+ T cells were unable to reinitiate cytokine production after a second Ag exposure. Furthermore, L. monocytogenes-specific CD8+ T cells in the same mice and lymphocytic choriomeningitis virus-specific CD8+ T cells in BALB\/c mice also underwent ON\/OFF cycling, but if the initial Ag stimulus was maximal, they could not produce IFN-\u03b3 after Ag re-exposure. As the initial Ag dose was reduced, the number of cells producing cytokine in response to the second Ag exposure exhibited a corresponding increase. However, T cells that were marked for IFN-\u03b3 secretion during the first stimulation did not contribute cytokine production during the second stimulation. Thus, T cells are not able to undergo rapid ON\/OFF\/ON cytokine cycling in vitro in response to Ag.<\/jats:p>","DOI":"10.4049\/jimmunol.174.2.718","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:32:54Z","timestamp":1398029574000},"page":"718-726","source":"Crossref","is-referenced-by-count":23,"title":["T Cells Undergo Rapid ON\/OFF but Not ON\/OFF\/ON Cycling of Cytokine Production in Response to Antigen"],"prefix":"10.1093","volume":"174","author":[{"given":"Gail A","family":"Corbin","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T","family":"Harty","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"},{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,1,15]]},"reference":[{"key":"2026020212240100700_R1","first-page":"593","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026020212240100700_R2","first-page":"217","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026020212240100700_R3","first-page":"891","volume-title":"Annu. Rev. Immunol.","year":"2004"},{"key":"2026020212240100700_R4","first-page":"783","volume-title":"Annu. Rev. Biochem.","year":"1990"},{"key":"2026020212240100700_R5","first-page":"275","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2026020212240100700_R6","first-page":"65","volume-title":"Annu. Rev. Immunol.","year":"2001"},{"key":"2026020212240100700_R7","first-page":"74","volume-title":"J. Mol. Med.","year":"2000"},{"key":"2026020212240100700_R8","first-page":"87","volume-title":"Curr. Opin. Microbiol.","year":"2002"},{"key":"2026020212240100700_R9","first-page":"37","volume-title":"Nat. Rev. Immunol.","year":"2002"},{"key":"2026020212240100700_R10","first-page":"76","volume-title":"Nature","year":"1999"},{"key":"2026020212240100700_R11","first-page":"5387","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020212240100700_R12","first-page":"451","volume-title":"Immunity","year":"2000"},{"key":"2026020212240100700_R13","first-page":"107","volume-title":"J. Immunol. Methods","year":"2000"},{"key":"2026020212240100700_R14","first-page":"749","volume-title":"Annu. Rev. Immunol.","year":"1997"},{"key":"2026020212240100700_R15","first-page":"491","volume-title":"Cell","year":"2004"},{"key":"2026020212240100700_R16","first-page":"2875","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026020212240100700_R17","first-page":"3402","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020212240100700_R18","first-page":"1877","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020212240100700_R19","first-page":"353","volume-title":"Immunity","year":"1998"},{"key":"2026020212240100700_R20","first-page":"777","volume-title":"Cell","year":"1988"},{"key":"2026020212240100700_R21","first-page":"2565","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020212240100700_R22","first-page":"2196","volume-title":"Infect. Immun.","year":"2000"},{"key":"2026020212240100700_R23","first-page":"1921","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2026020212240100700_R24","first-page":"1859","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020212240100700_R25","first-page":"665","volume-title":"Immunity","year":"2000"},{"key":"2026020212240100700_R26","first-page":"208","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020212240100700_R27","first-page":"913","volume-title":"Nat. Med.","year":"2001"},{"key":"2026020212240100700_R28","first-page":"4911","volume-title":"J. Virol.","year":"2003"},{"key":"2026020212240100700_R29","first-page":"221","volume-title":"Immunol. Rev.","year":"2002"},{"key":"2026020212240100700_R30","first-page":"4875","volume-title":"J. Immunol.","year":"2004"},{"key":"2026020212240100700_R31","first-page":"1528","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020212240100700_R32","first-page":"835","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026020212240100700_R33","first-page":"733","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026020212240100700_R34","first-page":"173","volume-title":"Scand. J. Immunol.","year":"2000"},{"key":"2026020212240100700_R35","first-page":"207","volume-title":"Annu. Rev. Immunol.","year":"1996"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/174\/2\/718\/62611723\/718.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/174\/2\/718\/62611723\/718.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T17:30:44Z","timestamp":1770053444000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/174\/2\/718\/8036682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2005,1,15]]},"published-print":{"date-parts":[[2005,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.174.2.718","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,1]]},"published":{"date-parts":[[2005,1]]}}}