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J. Virol. doi:10.1128/JVI.01581-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Spontaneous Recovery in Acute Human HCV Infection: Functional T Cell Thresholds and Relative Importance of CD4 Help

Division of Gastroenterology & Hepatology, Hepatitis C Center, and Integrated Program in Immunology; Department of Medicine, Division of Clinical Immunology; University of Colorado Health Sciences Center & National Jewish Hospital; Department of Virology, Hôpital Henri Mondor

^* To whom correspondence should be addressed. Email: Hugo.Rosen{at}UCHSC.edu.

	Abstract

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 viral 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 CTLs that can proliferate, exhibit cytotoxicity and produce IFN- does not ensure recovery, but whether these CTLs were primed in the presence or absence of CD4⁺ T-cell help (HCV-specific IL-2 production) is a critical determinant. These results have important implications for early prediction of virologic outcome following acute HCV and for the development of novel immunotherapeutic approaches.