IL-2- and STAT5-regulated cytokine gene expression in cells expressing the Tax protein of HTLV-1

Interleukin-2 (IL-2) mediates cell cycle progression and antiapoptosis in human T cells via several signal transduction pathways. The Tax protein of the human T-cell leukemia virus type I (HTLV-1) deregulates cell growth and alters the role of IL-2 in infected cells. However, Tax-immortalized cells stay dependent on IL-2, suggesting that events besides HTLV-1 gene expression are required for leukemia to develop. Here, IL-2-dependent and -independent events were analysed in a human T cell line immortalized by Tax. These studies show that, of the signaling pathways evaluated, only STAT5 remains dependent. Microarray analyses revealed several genes, including il-5, il-9 and il-13, are uniquely upregulated by IL-2 in the presence of Tax. Bioinformatics and supporting molecular biology show that some of these genes are STAT5 targets, explaining their IL-2 upregulation. These results suggest that IL-2 and viral proteins work together to induce gene expression, promoting the hypothesis that deregulation via the constitutive activation of STAT5 may lead to the IL-2-independent phenotype of HTLV-1-transformed cells.