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Journal of Virology, February 2008, p. 1827-1837, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.01581-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Spontaneous Recovery in Acute Human Hepatitis C Virus Infection: Functional T-Cell Thresholds and Relative Importance of CD4 Help{triangledown}

Susan Smyk-Pearson,1 Ian A. Tester,1 Jared Klarquist,1 Brent E. Palmer,3,4 Jean-Michel Pawlotsky,5 Lucy Golden-Mason,1,2,3 and Hugo R. Rosen1,2,3*

Division of Gastroenterology and Hepatology, Hepatitis C Center,1 Integrated Program in Immunology,2 Department of Medicine,3 Division of Clinical Immunology, University of Colorado Health Sciences Center and National Jewish Hospital, Denver, Colorado,4 Department of Virology, Hôpital Henri Mondor, Créteil, France5

Received 19 July 2007/ Accepted 15 November 2007

The mechanisms mediating protective immunity to hepatitis C virus (HCV) infection are incompletely understood because early infection in humans is rarely identified, particularly in those individuals who subsequently demonstrate spontaneous virus eradication. We have established a large national network of patients with acute HCV infection. Here, we comprehensively examined total HCV-specific CD4+ and CD8+ T-cell responses and identified functional T-cell thresholds that predict recovery. Interestingly, we found that the presence of HCV-specific cytotoxic T lymphocytes (CTLs) that can proliferate, exhibit cytotoxicity, and produce gamma interferon does not ensure recovery, but whether these CTLs were primed in the presence or absence of CD4+ T-cell help (HCV-specific interleukin-2 production) is a critical determinant. These results have important implications for early prediction of the virologic outcome following acute HCV and for the development of novel immunotherapeutic approaches.

* Corresponding author. Mailing address: GI and Hepatology Division, B-158, Academic Office Building 1, 12631 East 17th Ave., Room 7614, P.O. Box 6511, Aurora, CO 80045. Phone: (303) 724-1855. Fax: (303) 724-1891. E-mail: Hugo.Rosen{at}UCHSC.edu

{triangledown} Published ahead of print on 28 November 2007.

Journal of Virology, February 2008, p. 1827-1837, Vol. 82, No. 4
0022-538X/08/$08.00+0     doi:10.1128/JVI.01581-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Asabe, S., Wieland, S. F., Chattopadhyay, P. K., Roederer, M., Engle, R. E., Purcell, R. H., Chisari, F. V. (2009). The Size of the Viral Inoculum Contributes to the Outcome of Hepatitis B Virus Infection. J. Virol. 83: 9652-9662 [Abstract] [Full Text]  
  • Elsaesser, H., Sauer, K., Brooks, D. G. (2009). IL-21 Is Required to Control Chronic Viral Infection. Science 324: 1569-1572 [Abstract] [Full Text]  


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