Antiretroviral Therapy-Induced Dominant Interleukin-2 HIV-1 Gag CD4+ T Cell Response: Evidence of Functional Recovery of HIV-1-Specific CD4+ T Cells

Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV-1-specific T cells. However, it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral-specific immune response. To study this issue, we analysed the quantitative and qualitative differences of HIV-1-specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals. HIV-1 Gag and staphylococcal enterotoxin B (SEB)-reactive T cells were determined by flowcytometric intracellular secretion of IFN-gamma or/and L-2. ART resulted in increase of single IL-2 and decrease of single IFN-gamma-secreting HIV-1 CD4+ T cells, while both cytokines secreting HIV-1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL-2 and positively with single IFN-gamma-secreting HIV-1 CD4+ cells. Single IL-2 HIV-1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis, a dominant IL-2 HIV-1 CD4+ T cell response (> 70% single IL-2) was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV-1 CD4+ T cell responses were detected even in naive individuals with high viremia. In conclusion, the presence of dominant IL-2 HIV-1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL-2, indicates that the recovery of HIV-1-specific CD4+ T cell functionality under ART is a feasible goal. Furthermore, polyfunctional HIV-1 CD4+ T cell responses seem not to be directly involved in viral replication control.