{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:32:05Z","timestamp":1791221525379,"version":"4.1.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2003,2,1]],"date-time":"2003-02-01T00:00:00Z","timestamp":1044057600000},"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":[[2003,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD4 T cells are known to assist the CD8 T cell response by activating APC via CD40-CD40 ligand (L) interactions. However, recent data have shown that bacterial products can directly activate APC through Toll-like receptors, resulting in up-regulation of costimulatory molecules necessary for the efficient priming of naive T cells. It remains unclear what role CD4 T cell help and various costimulation pathways play in the development of CD8 T cell responses during bacterial infection. In this study, we examined these questions using an intracellular bacterium, Listeria monocytogenes, as a model of infection. In CD4 T cell-depleted, CD4\u2212\/\u2212, and MHC class II\u2212\/\u2212 mice, L. monocytogenes infection induced CD8 T cell activation and primed epitope-specific CD8 T cells to levels commensurate with those in normal C57BL\/6 mice. Furthermore, these epitope-specific CD8 T cells established long-term memory in CD4\u2212\/\u2212 mice that was capable of mounting a protective recall response. In vitro analysis showed that L. monocytogenes directly stimulated the activation and maturation of murine dendritic cells. The CD8 T cell response to L. monocytogenes was normal in CD40L\u2212\/\u2212 mice but defective in CD28\u2212\/\u2212 and CD137L\u2212\/\u2212 mice. These data show that in situations where infectious agents or immunogens can directly activate APC, CD8 T cell responses are less dependent on CD4 T cell help via the CD40-CD40L pathway but involve costimulation through CD137-CD137L and B7-CD28 interactions.<\/jats:p>","DOI":"10.4049\/jimmunol.170.4.2053","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:49:07Z","timestamp":1398109747000},"page":"2053-2063","source":"Crossref","is-referenced-by-count":122,"title":["Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During\n                    <i>Listeria monocytogenes<\/i>\n                    Infection"],"prefix":"10.1093","volume":"170","author":[{"given":"Devon J","family":"Shedlock","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K","family":"Whitmire","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Tan","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,2,15]]},"reference":[{"key":"2026020210080228000_R1","first-page":"5","volume-title":"Immunol. Rev.","year":"1997"},{"key":"2026020210080228000_R2","first-page":"1459","volume-title":"J. Exp. Med.","year":"1988"},{"key":"2026020210080228000_R3","first-page":"521","volume-title":"Cell","year":"1992"},{"key":"2026020210080228000_R4","first-page":"647","volume-title":"J. Cell Biol.","year":"1996"},{"key":"2026020210080228000_R5","first-page":"259","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020210080228000_R6","first-page":"2892","volume-title":"Infect. Immun.","year":"1991"},{"key":"2026020210080228000_R7","first-page":"53","volume-title":"Nature","year":"1993"},{"key":"2026020210080228000_R8","first-page":"S123","volume-title":"Infection","year":"1988"},{"key":"2026020210080228000_R9","first-page":"569","volume-title":"J. Immunol.","year":"1985"},{"key":"2026020210080228000_R10","first-page":"2005","volume-title":"J. Immunol.","year":"1987"},{"key":"2026020210080228000_R11","first-page":"3731","volume-title":"J. Immunol.","year":"1989"},{"key":"2026020210080228000_R12","first-page":"107","volume-title":"Immunology","year":"1990"},{"key":"2026020210080228000_R13","first-page":"869","volume-title":"J. Infect. Dis.","year":"1991"},{"key":"2026020210080228000_R14","first-page":"3116","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020210080228000_R15","first-page":"547","volume-title":"Science","year":"1993"},{"key":"2026020210080228000_R16","first-page":"1875","volume-title":"Infect. Immun.","year":"1992"},{"key":"2026020210080228000_R17","first-page":"S128","volume-title":"Infection","year":"1988"},{"key":"2026020210080228000_R18","first-page":"419","volume-title":"J. Theor. Biol.","year":"2001"},{"key":"2026020210080228000_R19","first-page":"166","volume-title":"Nat. Med.","year":"2002"},{"key":"2026020210080228000_R20","first-page":"480","volume-title":"Nature","year":"1998"},{"key":"2026020210080228000_R21","first-page":"478","volume-title":"Nature","year":"1998"},{"key":"2026020210080228000_R22","first-page":"474","volume-title":"Nature","year":"1998"},{"key":"2026020210080228000_R23","first-page":"3612","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020210080228000_R24","first-page":"5603","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R25","first-page":"5115","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R26","first-page":"1313","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R27","first-page":"481","volume-title":"Semin. Immunol.","year":"1998"},{"key":"2026020210080228000_R28","first-page":"6614","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210080228000_R29","first-page":"2320","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020210080228000_R30","first-page":"4833","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210080228000_R31","first-page":"3081","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020210080228000_R32","first-page":"2600","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020210080228000_R33","first-page":"47","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020210080228000_R34","first-page":"443","volume-title":"Immunity","year":"1999"},{"key":"2026020210080228000_R35","first-page":"2444","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R36","first-page":"3804","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020210080228000_R37","first-page":"25680","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020210080228000_R38","first-page":"423","volume-title":"Immunity","year":"1994"},{"key":"2026020210080228000_R39","first-page":"609","volume-title":"Science","year":"1993"},{"key":"2026020210080228000_R40","first-page":"3987","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2026020210080228000_R41","first-page":"521","volume-title":"J. Exp. Med.","year":"1984"},{"key":"2026020210080228000_R42","first-page":"8056","volume-title":"J. Virol.","year":"1994"},{"key":"2026020210080228000_R43","first-page":"1982","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R44","first-page":"77","volume-title":"J. Immunol. Methods","year":"1999"},{"key":"2026020210080228000_R45","first-page":"177","volume-title":"Immunity","year":"1998"},{"key":"2026020210080228000_R46","first-page":"8281","volume-title":"J. Virol.","year":"1998"},{"key":"2026020210080228000_R47","first-page":"158","volume-title":"Virology","year":"1998"},{"key":"2026020210080228000_R48","first-page":"6382","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210080228000_R49","first-page":"4504","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210080228000_R50","first-page":"1053","volume-title":"Eur. J. Immunol.","year":"2000"},{"key":"2026020210080228000_R51","first-page":"2924","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020210080228000_R52","first-page":"1877","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R53","first-page":"180","volume-title":"Nature","year":"1991"},{"key":"2026020210080228000_R54","first-page":"5620","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R55","first-page":"6991","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R56","first-page":"434","volume-title":"Infect. Immun.","year":"2002"},{"key":"2026020210080228000_R57","first-page":"499","volume-title":"Curr. Biol.","year":"1994"},{"key":"2026020210080228000_R58","first-page":"9762","volume-title":"J. Virol.","year":"2000"},{"key":"2026020210080228000_R59","first-page":"145","volume-title":"Nat. Immunol.","year":"2000"},{"key":"2026020210080228000_R60","first-page":"977","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210080228000_R61","first-page":"1735","volume-title":"Science","year":"2001"},{"key":"2026020210080228000_R62","first-page":"3402","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210080228000_R63","first-page":"415","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026020210080228000_R64","first-page":"423","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026020210080228000_R65","first-page":"448","volume-title":"Curr. Opin. Immunol.","year":"2000"},{"key":"2026020210080228000_R66","first-page":"3447","volume-title":"Eur. J. Immunol.","year":"2000"},{"key":"2026020210080228000_R67","first-page":"732","volume-title":"Nature","year":"2001"},{"key":"2026020210080228000_R68","first-page":"38","volume-title":"Immunology","year":"2002"},{"key":"2026020210080228000_R69","first-page":"740","volume-title":"Nature","year":"2000"},{"key":"2026020210080228000_R70","first-page":"1099","volume-title":"Nature","year":"2001"},{"key":"2026020210080228000_R71","first-page":"5037","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210080228000_R72","first-page":"4859","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210080228000_R73","first-page":"4897","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210080228000_R74","first-page":"536","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026020210080228000_R75","first-page":"4262","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210080228000_R76","first-page":"3777","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210080228000_R77","first-page":"521","volume-title":"Eur. J. Immunol.","year":"2002"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/4\/2053\/62566640\/2053.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/4\/2053\/62566640\/2053.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:10:07Z","timestamp":1770045007000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/170\/4\/2053\/8028299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2]]},"references-count":77,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2003,2,15]]},"published-print":{"date-parts":[[2003,2,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.170.4.2053","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,2]]},"published":{"date-parts":[[2003,2]]}}}