Increased susceptibility to CD8 T cell mediated killing limits the HIV-1 reservoir in naïve CD4 T cells from elite controllers (105.13)

Abstract

Abstract Elite controllers are HIV-1 infected persons with undetectable levels of HIV-1 replication in the absence of antiretroviral treatment, for reasons that remain unclear. We used a flow cytometric cytotoxicity assay based on the detection of Annexin V in dying target cells to assess the susceptibility of naïve and memory CD4 T cell subsets from elite controllers, HIV progressors, HAART-treated persons and HIV-1 negative individuals to killing by identical HIV-1-specific CD8 T cells. We found that naïve CD4 T cells from elite controllers showed significantly higher susceptibilities to HIV-1-specific CD8 T cell mediated killing than naïve CD4 T cells from all other reference patient cohorts. This increased susceptibility to CD8 T cell-dependent cytotoxicity was not related to higher baseline activation or apoptosis rates. Levels of integrated HIV-1 DNA were significantly decreased in naïve CD4 T cells from elite controllers compared to the alternative patient cohorts, while integrated HIV-1 DNA in memory cell subsets were not different between the study groups. Our data suggest that a higher susceptibility of naïve CD4 T cells to the cytotoxic activities of HIV-1-specific CD8 T cells reduces the HIV-1 reservoir in naïve T cells from elite controllers, and in this way contributes to low cellular reservoirs for HIV-1 in these patients.