| Author | Schulze zur Wiesch, Julian | |
| Author | Ciuffreda, Donatella | |
| Author | Lewis-Ximenez, Lia | |
| Author | Kasprowicz, Victoria | |
| Author | Nolan, Brian E. | |
| Author | Streeck, Hendrik | |
| Author | Aneja, Jasneet | |
| Author | Reyor, Laura L. | |
| Author | Allen, Todd M. | |
| Author | Lohse, Ansgar W, | |
| Author | McGovern, Barbara | |
| Author | Chung, Raymond T. | |
| Author | Kwok, William W. | |
| Author | Kim, Arthur Y. | |
| Author | Lauer, Georg M. | |
| Access date | 2017-01-17T19:50:48Z | |
| Available date | 2017-01-17T19:50:48Z | |
| Document date | 2012 | |
| Citation | 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. | pt_BR |
| ISSN | 0022-1007 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/16878 | |
| Language | eng | pt_BR |
| Publisher | The Rockfeller University Press | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Infecção aguda da Hepatite C | pt_BR |
| Subject in Portuguese | Terapia antiviral | pt_BR |
| 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 | pt_BR |
| Type | Article | |
| Abstract | 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. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatitis Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | MIT. Ragon institute. Boston, USA / Harvard Medical School. Massachusetts General Hospital. Boston, MA, USA. | pt_BR |
| Affilliation | Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA. | pt_BR |
| Affilliation | MIT. Ragon institute. Boston, USA / Harvard Medical School. Massachusetts General Hospital. Boston, MA, USA. | pt_BR |
| Affilliation | Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA / Harvard Medical School. Infected Disease Division. Boston, MA, USA, | pt_BR |
| Affilliation | Universitätsklinikum Hamburg Eppendorf. Medizinische Klinik. Hamburg, Germany | pt_BR |
| Affilliation | Tufts University Medical School. Lemuel Shattuck Hospital. Jamaica Plan, MA, USA. | pt_BR |
| Affilliation | Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA | pt_BR |
| Affilliation | Benaroya Research Institute at Virginia Mason.Seattle, WA, USA. | pt_BR |
| Affilliation | Harvard Medical School. Infected Disease Division. Boston, MA, USA, | pt_BR |
| Affilliation | Harvard Medical School. Gastrointestinal Unit. Boston, MA, USA. | pt_BR |
| Subject | acute hepatitis C infection | pt_BR |
| Subject | HCV-specific CD4+ T cell response | pt_BR |
| Subject | antiviral therapy | pt_BR |
| e-ISSN | 1540-9538 | |
