Heterogeneity in HIV Suppression by CD8 T Cells from HIV Controllers: Association with Gag-Specific CD8 T Cell Responses

"HIV controllers" (HICs) are rare individuals in whom HIV-1 plasma viral load remains undetectable without antiretroviral treatment. This spontaneous viral control in HICs is usually associated to strong functional HIV-specific CD8(+) T cell responses. Accordingly, we have recently shown that CD8(+) T cells from HICs strongly suppress ex vivo HIV-1 infection of autologous CD4(+) T cells, suggesting a crucial role of this response in vivo. Knowledge of the mechanisms underlying the CD8(+) T cell antiviral activity might help to develop effective T cell-based vaccines. In the present work, we further characterized the HIV-suppressive capacity of CD8(+) T cells in 19 HICs. CD8(+) T cells from 14 of the 19 HICs showed strong HIV-suppressive capacity ex vivo. This capacity was stable over time and was partially effective even on other primate lentiviruses. HIV-suppressive capacity of CD8(+) T cells correlated strongly with the frequency of HIV-specific CD8(+) T cells, and in particular of Gag-specific CD8(+) T cells. We also identified five HICs who had weak HIV-suppressive CD8(+) T cell capacities and HIV-specific CD8(+) T cell responses. Among these five HICs, at least three had highly in vitro replicative viruses, suggesting that the control of viremia in these patients is not due to replication-defective viruses. These results, on the one hand, suggest the importance of Gag responses in the antiviral potency of CD8(+) T cells from HICs and, on the other hand, propose that other host mechanisms may contribute to restraining HIV infection in HICs.