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Cytotoxic HIV-1 p55gag-Specific CD4+ T Cells Produce HIV-Inhibitory Cytokines and Chemokines

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Abstract

CD4+ T-helper cells appear to be essential in sustaining immune responses in chronic viral infections, as the maintenance of CD8+ cytotoxic T-lymphocyte responses and the control of viremia were demonstrated to depend on CD4+ T cell help. In order to investigate the function of HIV-specific CD4+ T cells in chronic HIV-1-infection, 49 chronically HIV-infected patients were analyzed before and 3 and 6 months after initiation of antiviral treatment. Ten patients showed a substantial, although weak, proliferative response to HIV-1-p55gag protein for which no improvement was observed upon initiation of HAART. From one individual, HIV-1-p55gag-specific CD4-positive T-cell clones were generated that were heterogeneous in their TCR Vβ gene usage and HLA-DRB1*13 and DRB1*03 restricted, respectively. In addition, some CD4+ TCC produced substantial amounts of IFN-γ and MIP-1α/β, were perforin-positive, and showed cytotoxic activity. These diverse functional features of HIV-specific CD4+ T cells suggest that they may exert direct antiviral activity.

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Authors and Affiliations

  1. Division of Allergology, Clinic for Rheumatology and Clinical Immunology/Allergology, University Hospital Bern, Switzerland

    Barbara Lotti, Thomas Wendland, Nikhil Yawalkar, Salome von Greyerz, Karin Schnyder & Werner J. Pichler

  2. Division of Infectious Diseases, University Hospital Bern, Switzerland

    Hansjakob Furrer

  3. Theodor Kocher Institute, Bern, Switzerland

    Marlène Brandes

  4. Kantonsspital St. Gallen, Switzerland

    Pietro Vernazza

  5. Institute of Medical Microbiology and Hygiene, University Regensburg, Germany

    Ralf Wagner

  6. AIDS Research Center, Massachusetts General Hospital, and, Harvard Medical School, Charlestown, Massachusetts, USA

    Thi Nguyen, Eric Rosenberg & Christian Brander

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  1. Barbara Lotti
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Lotti, B., Wendland, T., Furrer, H. et al. Cytotoxic HIV-1 p55gag-Specific CD4+ T Cells Produce HIV-Inhibitory Cytokines and Chemokines. J Clin Immunol 22, 253–262 (2002). https://doi.org/10.1023/A:1020066404226

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