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 genes that these lymphokines may specifically control and the interaction of these lymphokines in regulating the expression of their target genes. In this paper, we use the factor-dependent murine T cell line (CT.4R) 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 those grown in IL-4, but express similar levels of other cytoskeletal proteins including actin and tubulin. Vimentin was specifically induced by IL-2 and apparently suppressed by IL-4 in normal lymph node T cells, suggesting that its differential regulation by these lymphokines is physiologically relevant. We investigated the synergy between IL-2 and 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-2R alpha subunit. Complex regulatory interactions were revealed: IL-4 suppressed the ability of IL-2 to induce vimentin RNA but not IL-2R alpha RNA, whereas IL-2 inhibited the ability of IL-4 to induce lipase 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.
Hornbeck
P V
PV
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Garrels
J I
JI
Capetanaki
Y
Y
Heimer
S
S
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014746:Vimentin / Q000032:analysis / Q000235:genetics*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014746:Vimentin; D015847:Interleukin-4; D012313:RNA