ENHANCEMENT OF HIV-1 REPLICATION IN HUMAN MACROPHAGES IS INDUCED BY CD8(-CELL SOLUBLE FACTORS() T)

We previously reported that CD8(+) T cell-derived factors enhanced HIV long terminal repeat (LTR)mediated gene expression and replication in monocytic cell lines. We now report that replication of NSI and SI pr imary isolates of HIV-1 in human macrophages were significantly enhanc ed by CD8(+) T cell supernatants. The CD8-mediated enhancement of HIV replication was abrogated by pertussis toxin in a dose-dependent manne r. The sensitivity to pertussis toxin suggests that the CD8(+) T cell- derived enhancing factor is acting through a G protein-coupled signall ing pathway. Enhanced HIV replication in macrophages was accompanied b y increased levels of HIV-1 mRNA, suggesting that CD8 enhancement was mediated at the transcriptional level. interestingly, the replication of HIVBal, which replicates to high levels in macrophages, was not sig nificantly modulated by culture with CD8(+) T cell supernatants. Altho ugh direct co-culture of activated CD8(+) T cells with HIVAda-infected macrophages did not modulate replication, separation of the CD8(+) T cells from macrophages in transwell cultures resulted in significant e nhancement of replication. The inability to detect a modulatory effect in direct co-cultures appeared to be due to non-specific lysis of inf ected macrophages. Thus, soluble factors produced by CD8(+) T cells ex ert strong enhancing effects on HIV-1 replication in human macrophages .