Document 0347
 DOCN  M9440347
 TI    Cytokines from vaccine-induced HIV-1 specific cytotoxic T lymphocytes:
       effects on viral replication.
 DT    9404
 AU    Bollinger RC; Quinn TC; Liu AY; Stanhope PE; Hammond SA; Viveen R;
       Clements ML; Siliciano RF; Department of Medicine, Johns Hopkins
       University School of; Medicine, Baltimore, Maryland 21205.
 SO    AIDS Res Hum Retroviruses. 1993 Nov;9(11):1067-77. Unique Identifier :
       AIDSLINE MED/94145740
 AB    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.
 DE    AIDS Vaccines/IMMUNOLOGY  Clone Cells/IMMUNOLOGY
       Cytokines/*BIOSYNTHESIS/PHARMACOLOGY  Gene Expression Regulation,
       Viral/DRUG EFFECTS/IMMUNOLOGY  Gene Products, env/IMMUNOLOGY  Human
       HIV-1/GENETICS/*IMMUNOLOGY/PHYSIOLOGY  Protein Precursors/IMMUNOLOGY
       Support, U.S. Gov't, P.H.S.  T-Lymphocyte Subsets/IMMUNOLOGY
       T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  Tumor Necrosis Factor/PHARMACOLOGY
       T4 Lymphocytes/IMMUNOLOGY/MICROBIOLOGY  Virus Replication/DRUG
       EFFECTS/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).