Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence

Detalhes bibliográficos
Autor(a) principal: Schulze zur Wiesch, Julian
Data de Publicação: 2012
Outros Autores: Ciuffreda, Donatella, Lewis-Ximenez, Lia, Kasprowicz, Victoria, Nolan, Brian E., Streeck, Hendrik, Aneja, Jasneet, Reyor, Laura L., Allen, Todd M., Lohse, Ansgar W, McGovern, Barbara, Chung, Raymond T., Kwok, William W., Kim, Arthur Y., Lauer, Georg M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/16878
Resumo: Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA / Universitätsklinikum Hamburg Eppendorf. Medizinische Klinik. Hamburg, Germany / Heinrich Pette Institut-Leibniz Institute for Experimental Virology. Hamburg, Germany.
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spelling Schulze zur Wiesch, JulianCiuffreda, DonatellaLewis-Ximenez, LiaKasprowicz, VictoriaNolan, Brian E.Streeck, HendrikAneja, JasneetReyor, Laura L.Allen, Todd M.Lohse, Ansgar W,McGovern, BarbaraChung, Raymond T.Kwok, William W.Kim, Arthur Y.Lauer, Georg M.2017-01-17T19:50:48Z2017-01-17T19:50:48Z2012SCHULZE zur WIESCH, Julian; et al. Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence. J. Exp. Med., v.209, n.1, p.61-75, 2012.0022-1007https://www.arca.fiocruz.br/handle/icict/168781540-9538engThe Rockfeller University PressInfecção aguda da Hepatite CTerapia antiviralacute hepatitis C infectionHCV-specific CD4+ T cell responseantiviral therapyBroadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistenceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleHarvard Medical School. Gastrointestinal Unit. Boston, MA, USA / Universitätsklinikum Hamburg Eppendorf. Medizinische Klinik. Hamburg, Germany / Heinrich Pette Institut-Leibniz Institute for Experimental Virology. Hamburg, Germany.Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatitis Virais. Rio de Janeiro, RJ, Brasil.MIT. Ragon institute. Boston, USA / Harvard Medical School. Massachusetts General Hospital. Boston, MA, USA.Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA.MIT. Ragon institute. Boston, USA / Harvard Medical School. Massachusetts General Hospital. Boston, MA, USA.Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Infected Disease Division. Boston, MA, USA,Universitätsklinikum Hamburg Eppendorf. Medizinische Klinik. Hamburg, GermanyTufts University Medical School. Lemuel Shattuck Hospital. Jamaica Plan, MA, USA.Harvard Medical School. Gastrointestinal Unit. Boston, MA, USABenaroya Research Institute at Virginia Mason.Seattle, WA, USA.Harvard Medical School. Infected Disease Division. Boston, MA, USA,Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA.Vigorous proliferative CD4+ T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4+ T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4+ T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4+ T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4+ T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4+ T cells. Instead, broadly directed HCV-specific CD4+ T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T cell responses through antiviral therapy.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/16878/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALlia2_ximenez_etal_IOC_2012.pdflia2_ximenez_etal_IOC_2012.pdfapplication/pdf2230474https://www.arca.fiocruz.br/bitstream/icict/16878/2/lia2_ximenez_etal_IOC_2012.pdfa7e592e2054ae2006b235da509e3ba2fMD52TEXTlia2_ximenez_etal_IOC_2012.pdf.txtlia2_ximenez_etal_IOC_2012.pdf.txtExtracted texttext/plain80029https://www.arca.fiocruz.br/bitstream/icict/16878/3/lia2_ximenez_etal_IOC_2012.pdf.txtaacdb3dd13f1ee3ddb4b48e71b3cdab8MD53icict/168782018-08-15 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dc.title.pt_BR.fl_str_mv Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
title Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
spellingShingle Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
Schulze zur Wiesch, Julian
Infecção aguda da Hepatite C
Terapia antiviral
acute hepatitis C infection
HCV-specific CD4+ T cell response
antiviral therapy
title_short Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
title_full Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
title_fullStr Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
title_full_unstemmed Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
title_sort Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
author Schulze zur Wiesch, Julian
author_facet Schulze zur Wiesch, Julian
Ciuffreda, Donatella
Lewis-Ximenez, Lia
Kasprowicz, Victoria
Nolan, Brian E.
Streeck, Hendrik
Aneja, Jasneet
Reyor, Laura L.
Allen, Todd M.
Lohse, Ansgar W,
McGovern, Barbara
Chung, Raymond T.
Kwok, William W.
Kim, Arthur Y.
Lauer, Georg M.
author_role author
author2 Ciuffreda, Donatella
Lewis-Ximenez, Lia
Kasprowicz, Victoria
Nolan, Brian E.
Streeck, Hendrik
Aneja, Jasneet
Reyor, Laura L.
Allen, Todd M.
Lohse, Ansgar W,
McGovern, Barbara
Chung, Raymond T.
Kwok, William W.
Kim, Arthur Y.
Lauer, Georg M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Schulze zur Wiesch, Julian
Ciuffreda, Donatella
Lewis-Ximenez, Lia
Kasprowicz, Victoria
Nolan, Brian E.
Streeck, Hendrik
Aneja, Jasneet
Reyor, Laura L.
Allen, Todd M.
Lohse, Ansgar W,
McGovern, Barbara
Chung, Raymond T.
Kwok, William W.
Kim, Arthur Y.
Lauer, Georg M.
dc.subject.other.pt_BR.fl_str_mv Infecção aguda da Hepatite C
Terapia antiviral
topic Infecção aguda da Hepatite C
Terapia antiviral
acute hepatitis C infection
HCV-specific CD4+ T cell response
antiviral therapy
dc.subject.en.pt_BR.fl_str_mv acute hepatitis C infection
HCV-specific CD4+ T cell response
antiviral therapy
description Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA / Universitätsklinikum Hamburg Eppendorf. Medizinische Klinik. Hamburg, Germany / Heinrich Pette Institut-Leibniz Institute for Experimental Virology. Hamburg, Germany.
publishDate 2012
dc.date.issued.fl_str_mv 2012
dc.date.accessioned.fl_str_mv 2017-01-17T19:50:48Z
dc.date.available.fl_str_mv 2017-01-17T19:50:48Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SCHULZE zur WIESCH, Julian; et al. Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence. J. Exp. Med., v.209, n.1, p.61-75, 2012.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/16878
dc.identifier.issn.pt_BR.fl_str_mv 0022-1007
dc.identifier.eissn.none.fl_str_mv 1540-9538
identifier_str_mv SCHULZE zur WIESCH, Julian; et al. Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence. J. Exp. Med., v.209, n.1, p.61-75, 2012.
0022-1007
1540-9538
url https://www.arca.fiocruz.br/handle/icict/16878
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv The Rockfeller University Press
publisher.none.fl_str_mv The Rockfeller University Press
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/16878/2/lia2_ximenez_etal_IOC_2012.pdf
https://www.arca.fiocruz.br/bitstream/icict/16878/3/lia2_ximenez_etal_IOC_2012.pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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