Inhibition of cellular proliferation in human T lyophotropic virus type I (HTLV-I)-infected T cells from patients with HAM by steroid hormones and cyclosporin A.

The effects of steroid hormones and Cyclosporin A (CsA) on de novo DNA synthesis in four human T lymphotropic virus type I (HTLV-I)-infected T cell lines from patients with HTLV-I-associated myelopathy (HAM) were investigated. These T cell lines were characterized by helper/inducer phenotypes and expressed IL-2-receptor (Tac) and HLA-DR antigen in high percentages. Three of the four cell lines had their de novo DNA synthesis inhibited by steroid hormones (dexamethasone and 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3)) and CsA in a dose dependent manner. The inhibitory effects arose 24 hours after initiation of incubation with either steroid hormones or CsA. The forth cell line was not inhibited by these reagents. It also revealed through the use of an in vitro assay utilizing the human IL-2 dependent cell line, Sez 627, that none of these T cell lines secrete IL-2 in detectable volumes. In order to clarify the mechanism of the inhibitory effects of steroid hormones and CsA, among these 4 cell lines H-89-59, insensitive to the reagents, and H-109, sensitive to them, were used for northern blotting analysis. C-myc gene expression was demonstrated both in H-89-59 and H-109. 1,25(OH)2D3 and CsA suppressed c-myc expression in H-109 as well as cell proliferation. In H-89-59, however, neither expression of c-myc nor cell proliferation was suppressed. On the other hand, the level of HTLV-I gene transcripts was not changed by these agents. Hence, inhibition of cellular proliferation by these reagents was not caused by the inhibition of HTLV-I p40(x) gene but by inhibition of transcriptional factors such as c-myc products.