Heterogeneity in HIV suppression by CD8 T cells from HIV controllers: association with Gag-specific CD8 T cell responses

A Sáez-Cirión, M Sinet, SY Shin, A Urrutia… - The Journal of …, 2009 - journals.aai.org
A Sáez-Cirión, M Sinet, SY Shin, A Urrutia, P Versmisse, C Lacabaratz, F Boufassa…
The Journal of Immunology, 2009journals.aai.org
Abstract “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 …
Abstract
“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.
journals.aai.org