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
Yamada, H.; Nakao, Y.; Fujita, T.
Kobe Journal of Medical Sciences 37(2): 57-79
1991
ISSN/ISBN: 0023-2513 PMID: 1921263 Document Number: 379416
The effects of steroid hormones and cyclosporin A (CsA) on de nova DNA synthesis in four human T lymphotrophic 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 (dexamethason 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 fourth 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 volmes. 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 as well as cell proliferation. In H-89-59, however, neither expression of c-myc nor cell proliferation was supressed. 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 (.times.) gene but by inhibition of transcriptional factors such as c-myc products.