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 (M phi) 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 M phi leads to virus production, CD8(+) cells inhibited HIV replication when separated from the infected M phi by a transwell filter insert, indicating a diffusible factor made by the CD8(+) cells suppressed productive infection of M phi. Three beta-chemokines, which can be secreted by activated CD8(+) cells, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta prevented HIV replication in the M phi cultures, In addition, incubation of acutely infected M phi with a mixture of neutralizing antibodies to RANTES, MIP-1 alpha, and MIP-1 beta enhanced virus replication, Nevertheless, neutralization of beta-chemokines with specific antibodies did not abolish the suppression by CD8(+) cells of HIV replication in M phi. Thus, even though beta-chemokines decrease HIV replication in M phi, these cytokines are not responsible for the ability of CD8(+) cells to inhibit HIV production in these cells.