Anti-viral and immunomodulatory effects of interferon-alpha on cultured lymphocytes from patients with human T lymphotropic virus type I-associated myelopathy (HAM/TSP).
In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the mechanisms underlying its clinical efficacy. To investigate the anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I infection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomena were evaluated. In vitro activation of HTLV-I in fractionated CD4+ T lymphocyte-rich cells (CD4+ cells) could be demonstrated by increased thymidine incorporation into the cells, detection of proviral HTLV-I and viral RNA, and by assays of reverse transcriptase activities in culture supernatants. T cell immune responses were evaluated by thymidine incorporation into CD8+ T lymphocyte-rich cells (CD8+ cells) responding to cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens. It could be shown that IFN-alpha suppressed both the in vitro activation of HTLV-I and the CD8+ cell response. Moreover, 1 day supplementation of IFN-alpha as a pretreatment was sufficient for the induction of these properties. These findings, together with the clinical efficacy of IFN-alpha administration in patients with HAM/TSP, support the view that viral activation and T cell responses are critical components in the pathogenic processes involved in HAM/TSP.
Ijichi
S
S
Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
Izumo
S
S
Nagai
M
M
Shinmyozu
K
K
Hall
W W
WW
Osame
M
M
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015486:HTLV-I Antigens / Q000032:analysis; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D012194:RNA-Directed DNA Polymerase / Q000032:analysis
D000998:Antiviral Agents; D017931:DNA Primers; D015486:HTLV-I Antigens; D016898:Interferon-alpha; D012194:RNA-Directed DNA Polymerase