ANTIVIRAL 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 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.