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

DSpace/Manakin Repository

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

Citable link to this page

 

 
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
Author: Schulze zur Wiesch, Julian; Ciuffreda, Donatella; Lewis-Ximenez, Lia; Nolan, Brian E.; Aneja, Jasneet; Reyor, Laura L.; Lohse, Ansgar W.; McGovern, Barbara; Kwok, William W.; Kasprowicz, Victoria Olivia; Streeck, Hendrik; Allen, Todd; Chung, Raymond Taeyong; Kim, Arthur Yu-Shin; Lauer, Georg

Note: Order does not necessarily reflect citation order of authors.

Citation: Schulze zur Wiesch, Julian, Donatella Ciuffreda, Lia Lewis-Ximenez, Victoria Kasprowicz, Brian E. Nolan, Hendrik Streeck, Jasneet Aneja, Laura L. Reyor, Todd M. Allen, Ansgar W. Lohse, Barbara McGovern, Raymond T. Chung, William W. Kwok, Arthur Y. Kim, and Georg M. Lauer. 2012. Broadly directed virus-specific cd4+ T cell responses are primed during acute hepatitis c infection, but rapidly disappear from human blood with viral persistence. The Journal of Experimental Medicine 209(1): 61-75.
Full Text & Related Files:
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.
Published Version: doi:10.1084/jem.20100388
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260872/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10445610
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters