Abstract
“Elite controllers” are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals’ CD8
+
cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8
+
cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8
+
T cells expanded up to 2,500-fold above predepletion levels. This wave of CD8
+
T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8
+
NK cell frequencies changed no more than threefold. Together, our data suggest that CD8
+
T cells targeting a small number of epitopes, along with broad CD4
+
T-cell responses, can successfully control the replication of the AIDS virus. It is likely that subdominant CD8
+
T-cell populations play a key role in maintaining this control.
