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Science 24 October 2003:
Vol. 302. no. 5645, pp. 659 - 662
DOI: 10.1126/science.1088774
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Reports

HCV Persistence and Immune Evasion in the Absence of Memory T Cell Help

Arash Grakoui,1 Naglaa H. Shoukry,2 David J. Woollard,2 Jin-Hwan Han,1 Holly L. Hanson,1 John Ghrayeb,3 Krishna K. Murthy,4 Charles M. Rice,1 Christopher M. Walker2,5*

Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex–restricted epitopes and failure to resolve HCV infection.

1 Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10021, USA.
2 Center for Vaccines and Immunity, Columbus Children's Research Institute, 700 Children's Drive, W503, Columbus, OH 43205, USA.
3 Centocor, Malvern, PA 19355, USA.
4 Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.
5 Department of Pediatrics, College of Medicine and Public Health, Ohio State University, Columbus, OH 43205, USA.

* To whom correspondence should be addressed. E-mail: walkerc{at}pediatrics.ohio-state.edu

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N. H. Shoukry, J. Sidney, A. Sette, and C. M. Walker (2004)
J. Immunol. 172, 483-492
   Abstract »    Full Text »    PDF »
Progress in Defining CD4 Helper Cell Responses in Chronic Viral Infections.
C. L. Day and B. D. Walker (2003)
J. Exp. Med. 198, 1773-1777
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Science. ISSN 0036-8075 (print), 1095-9203 (online)