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Functional signatures of protective antiviral T-cell immunity in human virus infections

Authors

  • Alexandre Harari,

    1. Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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  • Valérie Dutoit,

    1. Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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  • Cristina Cellerai,

    1. Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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  • Pierre-Alexandre Bart,

    1. Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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  • Renaud A. Du Pasquier,

    1. Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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  • Giuseppe Pantaleo

    Corresponding author
    1. Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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Giuseppe Pantaleo, MD
Laboratory of AIDS Immunopathogenesis
Division of Immunology and Allergy
Centre Hospitalier Universitaire Vaudois
Rue Bugnon
1011 Lausanne
Switzerland
Tel.: +41 21 3141071
Fax: +41 21 3141070
E-mail: giuseppe.pantaleo@chuv.ch

Abstract

Summary:  The most common human viruses have different abilities to establish persistent chronic infection. Virus-specific T-cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus-specific CD4+ and CD8+ T-cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T-cell responses against different viruses. The heterogeneity of the T-cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4+ and CD8+ T-cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T-cell response within the same virus infection. Furthermore, the functional characterization of virus-specific CD4+ and CD8+ T-cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin-2 and interferon-γ (IFN-γ) secretion and proliferation, and not monofunctional, i.e. IFN-γ secretion, CD4+ and CD8+ T-cell responses represent correlates of protective antiviral immunity in chronic virus infections.

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