{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:28:35Z","timestamp":1791062915517,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"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":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Peptide vaccination induces T cell activation and cytotoxic T cell development. In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems. 4-1BBL-deficient (\u2212\/\u2212) and wild-type (+\/+) mice were immunized with a lipidated lymphocytic choriomeningitis virus (LCMV) peptide NP396\u2013404. Analysis of peptide-specific responses early after immunization by CTL assay, intracellular IFN-\u03b3 staining, and IFN-\u03b3 enzyme-linked immunospot assay (ELISPOT) indicated that CD8 T cell responses were reduced 3- to 10-fold in the absence of 4-1BB costimulation. Moreover, when agonistic anti-4-1BB Ab was given, CD8 T cell responses in 4-1BBL\u2212\/\u2212 mice were augmented to levels similar to those in 4-1BBL+\/+ mice. Two months after immunization, 4-1BBL+\/+ mice still had epitope-specific cells and were protected against viral challenge, demonstrating that peptide vaccination can induce long-term protection. In fact, 70% of CD8 T cells were specific for the immunizing peptide after viral challenge, demonstrating that strong, epitope-specific CD8 T cell responses are generated after peptide vaccination. In contrast, peptide-immunized 4-1BBL\u2212\/\u2212 mice had fewer epitope-specific cells and were impaired in their ability to resolve the infection. These results show that immunization with a single LCMV peptide provides long term protection against LCMV infection and point to costimulatory molecules such as 4-1BB as important components for generating protective immunity after vaccination.<\/jats:p>","DOI":"10.4049\/jimmunol.164.5.2320","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:48:34Z","timestamp":1398109714000},"page":"2320-2325","source":"Crossref","is-referenced-by-count":86,"title":["4-1BB Costimulation Is Required for Protective Anti-Viral Immunity After Peptide Vaccination"],"prefix":"10.1093","volume":"164","author":[{"given":"Joyce T","family":"Tan","sequence":"first","affiliation":[{"name":"The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine , Atlanta, GA 30322"}],"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":"Kaja","family":"Murali-Krishna","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":"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":"John D","family":"Altman","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":"Robert S","family":"Mittler","sequence":"additional","affiliation":[{"name":"The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine , Atlanta, GA 30322"},{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Epimmune , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C","family":"Pearson","sequence":"additional","affiliation":[{"name":"The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P","family":"Larsen","sequence":"additional","affiliation":[{"name":"The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"2026020213173763100_R1","first-page":"2242","volume-title":"Eur. 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