Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific cytotoxic T lymphocytes by pentoxifylline.
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.
Heinkelein
M
M
Institute for Virology and Immunobiology, Würzburg University, Germany.
Schneider-Schaulies
J
J
Walker
B D
BD
Jassoy
C
C
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000737:chemistry; D015488:HIV Antigens / Q000737:chemistry; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D014764:Viral Proteins; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D015683:Gene Products, gag; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D018799:Intercellular Adhesion Molecule-1; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D010431:Pentoxifylline