Comparative analysis of the capacity of elite suppressor CD4⁺ and CD8⁺ T cells to inhibit HIV-1 replication in monocyte-derived macrophages

Elite controllers or suppressors (ESs) are HIV-1-infected individuals who are able to maintain viral loads below the limit of detection of clinical assays without antiretroviral therapy. The mechanisms of virologic control are not fully understood, but ESs have been shown to have a more effective CD8⁺ T cell response to infected CD4⁺ T cells than chronic progressors (CPs). While macrophages are another cell type productively infected by HIV-1, few studies have examined the ability of primary effector T cells to suppress HIV-1 replication in these target cells. Here, we compared the ability of unstimulated primary CD4⁺ and CD8⁺ effector T cells to suppress viral replication in monocyte-derived macrophages (MDMs) in ESs and CPs. While CD4⁺ effector T cells were capable of inhibiting viral replication in MDMs, the magnitude of this response was not significantly different between ESs and CPs. In contrast, the CD8⁺ T cells from ESs were significantly more effective than those from CPs at inhibiting viral replication in MDMs. The CD4⁺ T cell response was partially mediated by soluble factors, while the CD8⁺ T cell response required cell-to-cell interaction. Our results suggest that the individual contributions of various effector cells should be considered in rational vaccine design and in ongoing eradication efforts.