title: Cytotoxic HIV-1 p55gag-specific CD4+ T cells produce HIV-inhibitory cytokines and chemokines.
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 Vbeta gene usage and HLA-DRB1*13 and DRB1*03 restricted, respectively. In addition, some CD4+ TCC produced substantial amounts of IFN-gamma and MIP-1alpha/beta 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.
authors.affiliation: Clinic for Rheumatology and Clinical Immunology/Allergology, University Hospital Bern, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lotti
authors.forename: Thomas
authors.initials: T
authors.lastname: Wendland
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Nikhil
authors.initials: N
authors.lastname: Yawalkar
authors.forename: Salome
authors.initials: S
authors.lastname: von Greyerz
authors.forename: Karin
authors.initials: K
authors.lastname: Schnyder
authors.forename: Marlène
authors.initials: M
authors.lastname: Brandes
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Thi
authors.initials: T
authors.lastname: Nguyen
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenberg
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology; D006801:Humans; D011498:Protein Precursors / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D018925:Chemokines; D016207:Cytokines; D000939:Epitopes; D015683:Gene Products, gag; D011498:Protein Precursors; D011948:Receptors, Antigen, T-Cell; C059767:p55 gag precursor protein, Human immunodeficiency virus 1