ANTIVIRAL AND IMMUNOMODULATORY EFFECTS OF INTERFERON-ALPHA ON CULTURED LYMPHOCYTES FROM PATIENTS WITH HUMAN-T-LYMPHOTROPIC VIRUS TYPE-I-ASSOCIATED MYELOPATHY (HAM TSP)/
S. Ijichi et al., ANTIVIRAL AND IMMUNOMODULATORY EFFECTS OF INTERFERON-ALPHA ON CULTURED LYMPHOCYTES FROM PATIENTS WITH HUMAN-T-LYMPHOTROPIC VIRUS TYPE-I-ASSOCIATED MYELOPATHY (HAM TSP)/, Journal of neuroimmunology, 61(2), 1995, pp. 213-221
In contrast to therapeutic benefits of interferon-alpha (IFN-alpha) in
patients with human T lymphotropic virus type I (HTLV-I)-associated m
yelopathy/tropical spastic paraparesis (HAM/TSP), little is known abou
t the mechanisms underlying its clinical efficacy. To investigate the
anti-viral and/or immunomodulatory properties of IFN-alpha in HTLV-I i
nfection, the effects of IFN-alpha on HTLV-I-induced in vitro phenomen
a were evaluated. In vitro activation of HTLV-I in fractionated CD4(+)
T lymphocyte-rich cells (CD4(+) cells) could be demonstrated by incre
ased thymidine incorporation into the cells, detection of proviral HTL
V-I and viral RNA, and by assays of reverse transcriptase activities i
n culture supernatants, T cell immune responses were evaluated by thym
idine incorporation into CD8(+) T lymphocyte-rich cells (CD8(+) cells)
responding to cultured and irradiated autologous CD4(+) cells possess
ing HTLV-I antigens. It could be shown that IFN-alpha suppressed both
the in vitro activation of HTLV-I and the CD8(+) cell response. Moreov
er, 1 day supplementation of IFN-alpha as a pretreatment was sufficien
t for the induction of these properties. These findings, together with
the clinical efficacy of IFN-alpha administration in patients with HA
M/TSP, support the view that viral activation and T cell responses are
critical components in the pathogenic processes involved in HAM/TSP.