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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4424-4432. Prepublished online as a Blood First Edition Paper on February 14, 2006; DOI 10.1182/blood-2005-09-3903. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-09-3903v1 107/11/4424    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Manigold, T. Articles by Rehermann, B. Search for Related Content PubMed PubMed Citation Articles by Manigold, T. Articles by Rehermann, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 30, 2005 Accepted January 12, 2006 Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees recovered from Hepatitis C Tobias Manigold, Eui-Cheol Shin, Eishiro Mizukoshi, Kathleen Mihalik, Krishna K Murthy, Charles M Rice, Ciriaco A Piccirillo, and Barbara Rehermann* Immunology Section, Liver Diseases Branch, NIDDK, NIH, DHHS, Bethesda, MD, USA Laboratory of Hepatitis Viruses, CBER, FDA, Bethesda, MD, USA Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX, USA The Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, USA Laboratory of Immunology NIH, DHHS, MD, USA and Department of Microbiology & Immunology, McGill University, Montreal, Canada * Corresponding author; email: Rehermann{at}nih.gov. Hepatitis C virus (HCV) poses a global health problem, because it readily establishes persistent infection and a vaccine is not available. CD4+CD25+ T cells have been implicated to contribute to HCV persistence, because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN--production by HCV-specific T cells. Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3+CD4+CD25+TReg cells and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-infected chimpanzees. Foxp3+CD4+CD25+TReg cells suppressed IFN--production, expansion and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection. Thus, TRegs control HCV-specific T cells not only in persistent infection but also after recovery, where they may regulate memory T cell responses by controlling their activation and preventing apoptosis. However, Foxp3+CD4+CD25+TReg cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3+CD4+CD25+TReg cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T cell receptor excision circle content implying a history of in vivo proliferation. This result suggests that HCV infection alters the population of Foxp3+CD4+CD25+TReg cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Radziewicz, C. C. Ibegbu, H. Hon, M. K. Osborn, K. Obideen, M. Wehbi, G. J. Freeman, J. L. Lennox, K. A. Workowski, H. L. Hanson, et al. Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection J. Virol., October 15, 2008; 82(20): 9808 - 9822. [Abstract] [Full Text] [PDF] A. Dolganiuc and G. Szabo T cells with regulatory activity in hepatitis C virus infection: what we know and what we don't J. Leukoc. Biol., September 1, 2008; 84(3): 614 - 622. [Abstract] [Full Text] [PDF] H. Ebinuma, N. Nakamoto, Y. Li, D. A. Price, E. Gostick, B. L. Levine, J. Tobias, W. W. Kwok, and K.-M. Chang Identification and In Vitro Expansion of Functional Antigen-Specific CD25+ FoxP3+ Regulatory T Cells in Hepatitis C Virus Infection J. Virol., May 15, 2008; 82(10): 5043 - 5053. [Abstract] [Full Text] [PDF] S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer Natural Regulatory T Cells and Persistent Viral Infection J. Virol., January 1, 2008; 82(1): 21 - 30. [Full Text] [PDF] A. Clayton, J. P. Mitchell, J. Court, M. D. Mason, and Z. Tabi Human Tumor-Derived Exosomes Selectively Impair Lymphocyte Responses to Interleukin-2 Cancer Res., August 1, 2007; 67(15): 7458 - 7466. [Abstract] [Full Text] [PDF] E. Yurchenko, M. Tritt, V. Hay, E. M. Shevach, Y. Belkaid, and C. A. Piccirillo CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence J. Exp. Med., October 30, 2006; 203(11): 2451 - 2460. [Abstract] [Full Text] [PDF]

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