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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3199-3207. Prepublished online as a Blood First Edition Paper on August 11, 2009; DOI 10.1182/blood-2009-03-208736. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2009-03-208736v1 114/15/3199    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Zelinskyy, G. Articles by Dittmer, U. PubMed PubMed Citation Articles by Zelinskyy, G. Articles by Dittmer, U. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response Gennadiy Zelinskyy1,*, Kirsten K. Dietze1,*, Yvonne P. Hüsecken1, Simone Schimmer1, Savita Nair1, Tanja Werner1, Kathrin Gibbert1, Olivia Kershaw2, Achim D. Gruber2, Tim Sparwasser3, and Ulf Dittmer1 1 Institute for Virology of the University Clinics in Essen, University of Duisburg-Essen, Essen; 2 Institute for Animal Pathology, Free University of Berlin, Berlin; and 3 Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany Cytotoxic CD8+ T cells control acute viremia in many viral infections. However, most viruses that establish chronic infections evade destruction by CD8+ T cells, and regulatory T cells (Treg) are thought to be involved in this immune evasion. We have infected transgenic mice, in which Treg can be selectively depleted, with Friend retrovirus (FV) to investigate the influence of Treg on pathogen-specific CD8+ T-cell responses in vivo. We observed that Treg expansion during acute infection was locally defined to organs with high viral loads and massive activation of virus-specific effector CD8+ T cells. Experimental ablation of Treg resulted in a significant increase of peak cytotoxic CD8+ T-cell responses against FV. In addition, it prevented the development of functional exhaustion of CD8+ T cells and significantly reduced FV loads in lymphatic organs. Surprisingly, despite the massive virus-specific CD8+ T-cell response after temporary Treg depletion, no evidence of immunopathology was found. These results demonstrate the important role of Treg in controlling acute retrovirus-specific CD8+ T-cell responses, and suggest that temporary manipulation of Treg might be a possible therapeutic approach in chronic infectious diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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