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M9620851.TXT
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1996-02-26
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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).