VIMENTIN EXPRESSION IS DIFFERENTIALLY REGULATED BY IL-2 AND IL-4 IN MURINE T-CELLS

IL-2 and IL-4 are T cell growth factors that are produced by different T cell subsets and have distinct roles in lymphocyte biology. Despite their importance in the immune system, little is known about the gene s that these lymphokines may specifically control and the interaction of these lymphokines in regulating the expression of their target gene s. In this paper, we use the factor-dependent murine T cell line (CT.4 R) to investigate the interaction of IL-2 and IL-4 in regulating gene expression. We report that the intermediate filament protein vimentin is differentially regulated by these lymphokines. Cells grown in IL-2 typically express 10- to 20-fold more vimentin and vimentin RNA than t hose grown in IL-4, but express similar levels of other cytoskeletal p roteins including actin and tubulin. Vimentin was specifically induced by IL-2 and apparently suppressed by IL-4 in normal lymph node T cell s, suggesting that its differential regulation by these lymphokines is physiologically relevant. We investigated the synergy between IL-2 an d IL-4 in regulating the expression of vimentin RNA and compared it to that of two other lymphokine-responsive genes, pancreatic lipase and the IL-2Ralpha subunit. Complex regulatory interactions were revealed: IL-4 suppressed the ability of IL-2 to induce vimentin RNA but not IL -2Ralpha RNA, whereas IL-2 inhibited the ability of IL-4 to induce lip ase RNA. These results indicate that IL-2 and IL-4 can cross-regulate lymphokine-responsive genes and can simultaneously exert both positive and negative regulation of different genes within the same cell.