Previous studies suggested that the potent immunosuppressive activities of transforming growth factor-beta (TGF-beta) were mediated in part through the inhibition of IL-2-dependent S-phase progression and mitosis of activated T cells. To further investigate the mechanism of T cell growth inhibition by TGF-beta, two constitutively activated murine T cell clones were employed as defined model systems for the growth factor-dependent phase of T cell proliferation. The Th cell line, HT-2, proliferated in response to either IL-2 or IL-4, whereas the cytotoxic T cell line, CT6, exhibited strict dependence on IL-2 for growth stimulation. In both cell lines, picomolar concentrations of TGF-beta inhibited S-phase progression stimulated by IL-2 or IL-4. TGF-beta pretreatment decreased the expression of high affinity IL-2R on HT-2 cells, but not on CT6 cells. In contrast, IL-2-stimulated transferrin receptor expression was markedly inhibited by TGF-beta in both T cell lines. Analyses of growth factor-dependent specific mRNA accumulation revealed that TGF-beta exerted selective inhibitory effects on gene expression in HT-2 and CT6 cells. TGF-beta significantly reduced early (1 to 2 h) increases in c-myc mRNA levels stimulated by IL-2 or IL-4 in both cell lines. In HT-2 cells, TGF-beta pretreatment also inhibited the early increase in granulocyte-macrophage CSF mRNA stimulated by IL-2 or IL-4. The inhibition of c-myc and granulocyte-macrophage cyte-macrophage CSF gene expression by TGF-beta was explained, at least in part, by suppression of the growth factor-dependent transcriptional activation of these genes. These studies suggest that inhibition of c-myc gene transcription may play a fundamental role in the antiproliferative effect of TGF-beta on IL-2- or IL-4-stimulated T cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.