Transforming growth factor-β inhibits IL-4 and IFN-γ production by stimulated human T cells

• Published in: International immunology 1994-03, Vol.6 (3), p.469-475
• Main Authors: Hotter, Wolfgang, Kalthoff, Frank S., Pickl, Winfried F., Ebner, Christoph, Majdic, Otto, Kraft, Dietrich, Knapp, Walter
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Blotting, Northern; Clone Cells; cytokine synthesis; Cytokines - biosynthesis; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Miscellaneous; Regulatory factors and their cellular receptors; T cells; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Transforming Growth Factor beta - pharmacology; transforming growth factor-β; Tumor Cells, Cultured; tyrosine phosphorytation
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/6.3.469

The present study investigates the effect of transforming growth factor (TGF-β on the production of IL-4 and IFN-γ by the leukemia Th0 type cell line HUT78, by freshly Isolated human T cells, and by antigen specific human T cell clones. We found that IL-4 and IFN-β, but not IL-2, production by stimulated HUT78 cells was inhibited by TGF-β1. TGF-β1 also reduced the accumulation of IL-4 and IFN-γ specific mRNA in stimulated HUT78 cells. However, IL-2 and IL-7 co-stimulated IL-4 and IFN-γ production, whereas IL-1, IL-3, IL-5, IL-6, IL-8, tumor necrosis factor-α or granulocyte macrophage colony stimulating factor had no effect. Because IL-2 is an Important helper cytokine for the production of IL-4 and IFN-γ, we investigated whether signal transductlon through the IL-2 receptor is Impaired by TGF-β1. We found that tyrosine phosphorylatlon in response to IL-2 In HUT78 cells was strongly inhibited by a short prelncubatlon with TGF-β1. Evidence for an antagonistic role for TGF-β1 and IL-2 comes from the finding that high doses of IL-2 could partially overcome TGF-β1 mediated inhibition of IL-4 and IFN-γ production. Similar to Its effect on HUT78 cells, TGF-β1 also inhibited IL-4 and IFN-γ production by freshly Isolated T cells as well as by human T cell clones. Taken together, our experiments show that the IL-2 dependent cytokines IL-4 and IFN-γ are both negatively controlled by TGF-β under conditions where IL-2 production Is unaffected by a mechanism which partially involves an inhibition of IL-2/1L-2R signal transductlon. These data Identify TGF-β and IL-2 as mutual antagonists in the regulation of IL-4 and IFN-γ production.