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    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 (2009)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Zelinskyy, Gennadiy
    Dietze, Kirsten K
    Hüsecken, Yvonne P
    Schimmer, Simone
    Nair, Savita
    Werner, Tanja
    Gibbert, Kathrin
    Kershaw, Olivia
    Gruber, Achim D
    Sparwasser, Tim
    Dittmer, Ulf
    Quelle
    Blood; 114(15) — S. 3199–3207
    ISSN: 0006-4971
    Sprache
    Englisch
    Verweise
    DOI: 10.1182/blood-2009-03-208736
    Pubmed: 19671923
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    Abstract / Zusammenfassung

    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.