CD8+ cells from HIV-2-infected baboons control HIV replication

Objective: To analyze the CD8+ cell antiviral immune response in HIV-2-infected baboons. Design: Baboons were infected with clinical isolates of HIV-2. CD8+ cells were isolated from phytohemagglutinin (PHA)-stimulated baboon peripheral blood mononuclear cells (PBMC). These cells were cultured with PHA-stimulated CD4+ cells acutely infected with HIV-2 at several CD8+ : CD4+ cell ratios. Control of HIV-2 replication was determined by comparing peak levels of HIV-2 replication in fluids from CD8+ : CD4+ cell cocultures with those in fluids from infected CD4+ cells cultured alone. Results: CD8+ cells from HIV-2-infected baboons inhibited HIV-2 replication in acutely infected autologous CD4+ cells to a significantly greater extent than did CD8+ cells from uninfected baboons (P = 0.0001). At the beginning of the acute phase of HIV-2 infection, CD8+ cells showed either a transient reduction or loss in the antiviral activity. In some cases the CD8+ cell response enhanced HIV-2 replication. Subsequently, the strength of the CD8+ cell antiviral activity increased concomitant with a decrease in the HIV-2 load in the PBMC. Suppression of HIV replication could be demonstrated with filtered fluid from CD8+ cells. Other studies indicated that infected CD4+ cells are lost during coculture of CD8+ cells with infected CD4+ cells. Conclusions: CD8+ cells of HIV-2-infected baboons develop substantial anti-HIV-2 activity following HIV-2 infection, which may account in part for the low frequency of pathogenesis in HIV-2-infected baboons. Studies to elucidate the mechanism of this CD8+ cell antiviral activity suggest that it is mediated in part by a soluble antiviral factor, but primarily in association with the loss of infected CD4+ cells.