CD8+ T cell-mediated enhancement of tumour necrosis factor-alpha (TNF-alpha) production and HIV-1 LTR-driven gene expression in human monocytic cells is pertussis toxin-sensitive.
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-alpha. 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-alpha and was significantly abrogated by antibody to TNF-alpha. 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-alpha 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.
Copeland
K F
KF
Centre for Molecular Medicine, Ottawa General Hospital Research Institute, Ottawa, Canada. kcopeland@ogh.on.ca
McKay
P J
PJ
Newton
J
J
Rosenthal
K L
KL
D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D037342:Pertussis Toxin; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D015500:Chloramphenicol O-Acetyltransferase; D037342:Pertussis Toxin