Differential Effect of TGF-β1 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)

Abstract

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-β as a preferential immune regulator in the CNS and the functional heterogeneity of TGF-β has led us to assess the possible involvement of this cytokine in the pathogenic process. To investigate this, the modulatory effects of TGF-β1 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-β1. However, the in vitro activation of HTLV-I, which was evaluated by spontaneous proliferation of CD4 + cells, was unaffected by TGF-βI. The induction of intracytoplasmic HTLV-I antigens in cultured CD4 + cells was facilitated by TGF-β1 in a dose-dependent manner. These findings suggest that TGF-β may have a critical role in localized viral activation within the CNS in patients with HAM/TSP.