CD8+T cell-mediated enhancement of tumour necrosis factor-alpha (TNF-α) production and HIV-1 LTR-driven gene expression in human monocytic cells is pertussis toxin-sensitive

摘要

HIV replication and LTR-mediated gene expression can be modulated by CD8+T cells in a cell type-dependent manner. We have previously shown that supernatants of activated CD8+ T cells of HIV-infected individuals greatly enhanced p24 levels in human macrophages infected with NSI or SI primary isolates of HIV-1. Here we have examined the effect of culture with CD8+T cell supernatants on HIV-1 LTR-mediated gene expression in monocytic cells. CD8+T cell supernatants enhanced LTR-mediated gene expression in U38 cells activated with Tat in the absence or presence of phorbol myristate acetate (PMA) and ionomycin or TNF-α. Further, enhancement of LTR-mediated gene expression and virus replication in U38 cells and U1 cells, respectively, was pertussis toxin-sensitive. The enhancement of gene expression and virus replication was associated with increased levels of TNF-α and was significantly abrogated by antibody to TNF-α. In contrast, the suppression of LTR-mediated gene expression by CD8+T cell supernatants in Jurkat T cells was not pertussis toxin-sensitive and TNF-α levels were not affected. These results demonstrate that factors produced by CD8+T cells utilize different cellular pathways to mediate their effects on HIV transcription and replication in different cell types.