Primary CD8(+) cells from HIV-infected individuals can suppress productive infection of macrophages independent of β-chemokines

The productive infection of human monocyte-derived macrophages (Mφ) by HIV was suppressed by primary CD8(+) cells from asymptomatic HIV-infected individuals. This anti-HIV response was noncytotoxic; removal of the CD8(+) cells from the infected Mφ leads to virus production. CD8(+) cells inhibited HIV replication when separated from the infected Mφ by a transwell filter insert, indicating a diffusible factor made by the CD8(+) cells suppressed productive infection of Mφ. Three β-chemokines, which can be secreted by activated CD8(+) cells, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1α and MIP-1β prevented HIV replication in the Mφ cultures. In addition, incubation of acutely infected Mφ with a mixture of neutralizing antibodies to RANTES, MIP-1α, and MIP-1β enhanced virus replication. Nevertheless, neutralization of β-chemokines with specific antibodies did not abolish the suppression by CD8(+) cells of HIV replication in Mφ. Thus, even though β-chemokines decrease HIV replication in Mφ, these cytokines are not responsible for the ability of CD8(+) cells to inhibit HIV production in these cells.