title: CD8+ T cell supernatants of HIV type 1-infected individuals have opposite effects on long terminal repeat-mediated transcription in T cells and monocytes.
abstract: CD8+ T lymphocytes of HIV-1-infected individuals can efficiently suppress HIV-1 replication in CD4+ T lymphocytes via soluble factors. We compared the effect of CD8+ T cell-derived supernatants on HIV-1 LTR-driven gene expression in T cells and monocytic cell lines. Our results demonstrate that CD8+ T cell supernatants that suppressed HIV-1 LTR-driven gene expression in Jurkat T cells significantly enhanced expression in Tat-activated U38 monocytic cells in the presence and absence of mitogenic stimulation. Examination of a panel of CD8+ T cell-derived supernatants form HIV-infected individuals demonstrated that the extent of enhancement of transcription in U38 cells was mirrored in most cases by a similar level of suppression of transcription in Jurkat T cells. In latently infected U1 cells treated with TNF-alpha, culture with CD8+ T cell supernatants markedly enhanced virus production. In addition, the percentage increase in the enhancement of HIV-1 LTR-driven CAT expression by CD8+ T cell supernatants correlated strongly (r = 0.911) with the level of p24 detected. The level of LTR-mediated gene expression in U38 cells was not influenced by rhMIP-1 alpha rhMIP-1 beta, or rhRANTES over a wide range of chemokine concentration. Treatment of CD8+ T cell supernatant with a combination of antibodies to these chemokines resulted in a further augmentation of LTR-mediated CAT expression in U38 cells. Taken together, these results demonstrate that CD8+ T cell suppressive factors may have opposite effects on HIV-1 LTR-driven gene expression and replication dependent on target cell type and further suggest that the beta-chemokines do not influence HIV-1 LTR-mediated gene expression in monocytic cells.
authors.affiliation: Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
authors.forename: K F
authors.initials: KF
authors.lastname: Copeland
authors.forename: J G
authors.initials: JG
authors.lastname: Leith
authors.forename: P J
authors.initials: PJ
authors.lastname: McKay
authors.forename: K L
authors.initials: KL
authors.lastname: Rosenthal
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology; D017077:Culture Media, Conditioned; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D016325:HIV Long Terminal Repeat / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000821:virology*; D009000:Monocytes / Q000821:virology*; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha