title: Cytokines from vaccine-induced HIV-1 specific cytotoxic T lymphocytes: effects on viral replication.
abstract: Cytolytic T lymphocytes (CTLs) specific for the human immunodeficiency virus (HIV-1) envelope glycoproteins have been cloned from HIV-1-seronegative human volunteers immunized with HIV-1 gp160-based candidate vaccines. Although vaccine-induced CTLs can potentially contribute to the antiviral response by direct lysis of infected cells, these CTLs may also produce cytokines that alter HIV-1 gene expression in other infected cells present in the microenvironment where CTL-target cell interactions occur. Vaccine-induced CTL clones were therefore examined for production of cytokines that affect HIV-1 gene expression in chronically infected T lymphocytic and promonocytic cell lines. Enhancement of HIV-1 gene expression was observed with supernatants from CD4+ CTL clones and with supernatants from a subset of CD8+ CTL clones. For each clone studied, upregulation of HIV-1 gene expression in chronically infected T cell lines resulted from the antigen-specific release by CTLs of tumor necrosis factor alpha (TNF-alpha). CD4+ and CD8+ CTLs that released TNF-alpha on antigen stimulation were also shown to express a biologically active 26-kDa transmembrane form of TNF-alpha, which was sufficient to induce upregulation of HIV-1 gene expression in chronically infected T cells placed in direct contact with the CTLs. Supernatants from antigen-activated, vaccine-induced CD4+ and CD8+ CTLs also caused upregulation of HIV-1 gene expression in chronically infected promonocytic cells. A subset of CD8+ CTL clones also produced a soluble factor(s) that inhibited HIV-1 replication in acutely infected autologous CD4+ blasts. Supernatants from CD4+ CTLs had no effect on HIV-1 replication in acutely infected CD4+ blasts. These results suggest that cytokine production as well as cytolytic activity should be evaluated in the analysis of the potential antiviral effects of vaccine-induced CTLs.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: R C
authors.initials: RC
authors.lastname: Bollinger
authors.forename: T C
authors.initials: TC
authors.lastname: Quinn
authors.forename: A Y
authors.initials: AY
authors.lastname: Liu
authors.forename: P E
authors.initials: PE
authors.lastname: Stanhope
authors.forename: S A
authors.initials: SA
authors.lastname: Hammond
authors.forename: R
authors.initials: R
authors.lastname: Viveen
authors.forename: M L
authors.initials: ML
authors.lastname: Clements
authors.forename: R F
authors.initials: RF
authors.lastname: Siliciano
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D011498:Protein Precursors / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha