       Document 0851
 DOCN  M9620851
 TI    Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific
       cytotoxic T lymphocytes by pentoxifylline.
 DT    9602
 AU    Heinkelein M; Schneider-Schaulies J; Walker BD; Jassoy C; Institute for
       Virology and Immunobiology, Wurzburg University,; Germany.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 1;10(4):417-24.
       Unique Identifier : AIDSLINE MED/96074274
 AB    HIV-specific cytotoxic T lymphocytes (CTLs) are an important component
       of the host immune response against HIV infection, and these cells
       release a variety of cytokines when they meet their target antigen.
       Since the phosphodiesterase inhibitor pentoxifylline is being used as a
       therapeutic agent in clinical trials of HIV infection due to its
       inhibitory effect on virus replication in vitro, we examined the effect
       of pentoxifylline on cytotoxicity and cytokine secretion by HIV-specific
       CD8+ CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppressed
       interferon-gamma, tumor necrosis factor-alpha, and
       granulocyte-macrophage colony-stimulating factor release by these cells
       at the transcription level. Suppression of cytokine release resulted in
       reduced capacity of the CTLs to induce HLA class I and ICAM-1 expression
       and to stimulate HIV-1 replication. These results suggest that
       inhibition of HIV-specific CD8+ CTLs by pentoxifylline may be
       therapeutically relevant. Moreover, this study extends previous
       observations by demonstrating that, in addition to its ability to
       suppress cytokine production by macrophages and CD4+ T helper cells,
       pentoxifylline may inhibit cytotoxicity and cytokine secretion by
       antigen-specific CD8+ cytotoxic T lymphocytes.
 DE    Amino Acid Sequence  Blotting, Northern  Cell Line
       Cytokines/*BIOSYNTHESIS  Cytotoxicity, Immunologic/*DRUG EFFECTS
       CD8-Positive T-Lymphocytes/DRUG EFFECTS/METABOLISM/*VIROLOGY  Flow
       Cytometry  Gene Products, gag/CHEMISTRY  Histocompatibility Antigens
       Class I/BIOSYNTHESIS  Human  HIV Antigens/CHEMISTRY  HIV-1/*PHYSIOLOGY
       Intercellular Adhesion Molecule-1/BIOSYNTHESIS  Molecular Sequence Data
       Pentoxifylline/*PHARMACOLOGY  Phosphodiesterase Inhibitors/*PHARMACOLOGY
       RNA-Directed DNA Polymerase/CHEMISTRY  RNA, Messenger/BIOSYNTHESIS
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes,
       Cytotoxic/DRUG EFFECTS/METABOLISM/*VIROLOGY  Virus Replication  JOURNAL
       ARTICLE

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

