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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 primary isolates of HIV-1 in human macrophages were significantly enhanced by CD8+ T cell supernatants. The CD8-mediated enhancement of HIV replication was abrogated by pertussis toxin in a dose-dependent manner. The sensitivity to pertussis toxin suggests that the CD8+ T cell-derived enhancing factor is acting through a G protein-coupled signalling pathway. Enhanced HIV replication in macrophages was accompanied by increased levels of HIV-1 mRNA, suggesting that CD8 enhancement was mediated at the transcriptional level. Interestingly, the replication of HIV(Bal), which replicates to high levels in macrophages, was not significantly modulated by culture with CD8+ T cell supernatants. Although direct co-culture of activated CD8+ T cells with HIV(Ada)-infected macrophages did not modulate replication, separation of the CD8+ T cells from macrophages in transwell cultures resulted in significant enhancement of replication. The inability to detect a modulatory effect in direct co-cultures appeared to be due to non-specific lysis of infected macrophages. Thus, soluble factors produced by CD8+ T cells exert strong enhancing effects on HIV-1 replication in human macrophages.

The effect of herpes simplex virus type 1 (HSV-1) infection on human cytotoxic T-lymphocyte (CTL) lytic function was assessed. All HSV-infected CTL populations tested were significantly inhibited in lysing target cells. The inhibition of CTL lytic function by infection with HSV-1 was independent of T-cell receptor-mediated antigen recognition and did not involve virus-induced shutoff of host protein synthesis, the expression of the HSV-1 transactivation protein, ICP4, or replicating virus. Understanding the functional impairment of CTL following infection with HSV may have important implications for HSV-induced immunosuppression and the mechanism of HSV persistence in immunocompetent hosts.