Cytotoxic HIV-1 p55gag-specific CD4+ T cells produce HIV-inhibitory cytokines and chemokines.
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.
Lotti
Barbara
B
Clinic for Rheumatology and Clinical Immunology/Allergology, University Hospital Bern, Switzerland.
Wendland
Thomas
T
Furrer
Hansjakob
H
Yawalkar
Nikhil
N
von Greyerz
Salome
S
Schnyder
Karin
K
Brandes
Marlène
M
Vernazza
Pietro
P
Wagner
Ralf
R
Nguyen
Thi
T
Rosenberg
Eric
E
Pichler
Werner J
WJ
Brander
Christian
C
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
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