DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Su-Hyung | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Capone, Stefania | ko |
dc.contributor.author | Caggiari, Laura | ko |
dc.contributor.author | De Re, Valli | ko |
dc.contributor.author | Nicosia, Alfredo | ko |
dc.contributor.author | Folgori, Antonella | ko |
dc.contributor.author | Rehermann, Barbara | ko |
dc.date.accessioned | 2013-03-13T04:59:49Z | - |
dc.date.available | 2013-03-13T04:59:49Z | - |
dc.date.created | 2012-11-02 | - |
dc.date.created | 2012-11-02 | - |
dc.date.issued | 2012-10 | - |
dc.identifier.citation | GASTROENTEROLOGY, v.143, no.4, pp.1048 - U296 | - |
dc.identifier.issn | 0016-5085 | - |
dc.identifier.uri | http://hdl.handle.net/10203/104516 | - |
dc.description.abstract | BACKGROUND & AIMS: T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells. METHODS: We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time polymerase chain reaction. RESULTS: In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies for a longer time after HCV challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death-1 (PD-1) than infection-induced T cells. Vaccine-induced, but not infection- induced, T cells were multifunctional; their ability to secrete interferon gamma and tumor necrosis factor alpha correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127(+) memory precursor phenotype was induced by the vaccine itself rather than by low viremia. In contrast, induction of PD-1 correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 messenger RNAs correlated with peak titers of HCV. CONCLUSIONS: Compared with infection, vaccination-induced HCV-specific CD127(+) T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented up-regulation of PD-1 on T cells and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1-PD-L1 pathway might be necessary components of successful vaccine-induced protection against HCV. | - |
dc.language | English | - |
dc.publisher | W B SAUNDERS CO-ELSEVIER INC | - |
dc.subject | IMMUNE-RESPONSES | - |
dc.subject | NEUTRALIZING ANTIBODY | - |
dc.subject | PROGRAMMED DEATH-1 | - |
dc.subject | CHRONIC INFECTION | - |
dc.subject | CHIMPANZEES | - |
dc.subject | EXPRESSION | - |
dc.subject | PERSISTENCE | - |
dc.subject | IMMUNIZATION | - |
dc.subject | DETERMINANTS | - |
dc.subject | PROTECTION | - |
dc.title | Successful Vaccination Induces Multifunctional Memory T-Cell Precursors Associated With Early Control of Hepatitis C Virus | - |
dc.type | Article | - |
dc.identifier.wosid | 000309361800036 | - |
dc.identifier.scopusid | 2-s2.0-84866733892 | - |
dc.type.rims | ART | - |
dc.citation.volume | 143 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 1048 | - |
dc.citation.endingpage | U296 | - |
dc.citation.publicationname | GASTROENTEROLOGY | - |
dc.identifier.doi | 10.1053/j.gastro.2012.06.005 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Capone, Stefania | - |
dc.contributor.nonIdAuthor | Caggiari, Laura | - |
dc.contributor.nonIdAuthor | De Re, Valli | - |
dc.contributor.nonIdAuthor | Nicosia, Alfredo | - |
dc.contributor.nonIdAuthor | Folgori, Antonella | - |
dc.contributor.nonIdAuthor | Rehermann, Barbara | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | CD8 (+) T Cells | - |
dc.subject.keywordAuthor | IFN | - |
dc.subject.keywordAuthor | TNF | - |
dc.subject.keywordAuthor | Vaccine Development | - |
dc.subject.keywordAuthor | CD127 | - |
dc.subject.keywordPlus | IMMUNE-RESPONSES | - |
dc.subject.keywordPlus | NEUTRALIZING ANTIBODY | - |
dc.subject.keywordPlus | PROGRAMMED DEATH-1 | - |
dc.subject.keywordPlus | CHRONIC INFECTION | - |
dc.subject.keywordPlus | CHIMPANZEES | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PERSISTENCE | - |
dc.subject.keywordPlus | IMMUNIZATION | - |
dc.subject.keywordPlus | DETERMINANTS | - |
dc.subject.keywordPlus | PROTECTION | - |
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