Cytotoxic HIV-1 p55 gag -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-p55 gag protein for which no improvement was observed upon initiation of HAART. From one individual, HIV-1-p55 gag -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.