Differential effect of TGF-beta 1 on the in vitro activation of HTLV-I and the proliferative response of CD8+ T lymphocytes in patients with HTLV-I-associated myelopathy (HAM/TSP).
While considerable information is available on the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), fundamental questions remain unanswered. In particular the clinicopathological uniformity of the disorder among patients remains poorly understood. The potential role of TGF-beta as a preferential immune regulator in the CNS and the functional heterogeneity of TGF-beta has led us to assess the possible involvement of this cytokine in the pathogenic process. To investigate this, the modulatory effects of TGF-beta 1 on HTLV-I-induced in vitro phenomena were evaluated using fractionated lymphocytes from patients with HAM/TSP. It could be shown that the proliferative response of CD8+ cells against cultured and irradiated autologous CD4+ cells possessing HTLV-I antigens was significantly inhibited by TGF-beta 1. However, the in vitro activation of HTLV-I, which was evaluated by spontaneous proliferation of CD4+ cells, was unaffected by TGF-beta 1. The induction of intracytoplasmic HTLV-I antigens in cultured CD4+ cells was facilitated by TGF-beta 1 in a dose-dependent manner. These findings suggest that TGF-beta may have a critical role in localized viral activation within the CNS in patients with HAM/TSP.
Nagai
M
M
Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
Ijichi
S
S
Hall
W W
WW
Osame
M
M
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*
D016212:Transforming Growth Factor beta