{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:16:51Z","timestamp":1781875011987,"version":"3.54.5"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"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":[[2014,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite the widespread use of replication-incompetent recombinant adenovirus (Ad) vectors as candidate vaccine platforms, the mechanism by which these vectors elicit CD8+ T cell responses remains poorly understood. Our data demonstrate that induction and maintenance of CD8+ T cell responses by Ad vector immunization is longitudinally dependent on CD4+ T cell help for a prolonged period. Depletion of CD4+ T cells in wild type mice within the first 8 d following Ad immunization resulted in dramatically reduced induction of Ag-specific CD8+ T cells, decreased T-bet and eomesodermin expression, impaired KLRG1+ effector differentiation, and atypical expression of the memory markers CD127, CD27, and CD62L. Moreover, these CD8+ T cells failed to protect against a lethal recombinant Listeria monocytogenes challenge. Depletion of CD4+ T cells between weeks 1 and 4 following immunization resulted in increased contraction of memory CD8+ T cells. These data demonstrate a prolonged temporal requirement for CD4+ T cell help for vaccine-elicited CD8+ T cell responses in mice. These findings have important implications in the design of vaccines aimed at eliciting CD8+ T cell responses and may provide insight into the impaired immunogenicity of vaccines in the context of AIDS and other CD4+ T cell immune deficiencies.<\/jats:p>","DOI":"10.4049\/jimmunol.1302806","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T07:24:55Z","timestamp":1398756295000},"page":"5214-5225","source":"Crossref","is-referenced-by-count":26,"title":["Longitudinal Requirement for CD4+ T Cell Help for Adenovirus Vector\u2013Elicited CD8+ T Cell Responses"],"prefix":"10.1093","volume":"192","author":[{"given":"Nicholas M","family":"Provine","sequence":"first","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael A","family":"Larocca","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Penaloza-MacMaster","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N","family":"Borducchi","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"McNally","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily R","family":"Parenteau","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan H","family":"Barouch","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center , Boston, MA 02215"},{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"2025032404321829900_r1","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nm.2447","article-title":"CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates","volume":"17","author":"Sullivan","year":"2011","journal-title":"Nat. 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