Transforming growth factor-beta (TGF-beta)-resistant helper T lymphocyte clones show a concomitant loss of all three types of TGF- beta receptors

• Published in: The Journal of immunology (1950) Vol. 146; no. 9; pp. 3063 - 3067
• Main Authors: Siepl, C, Malipiero, UV, Fontana, A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.05.1991; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Blotting, Northern; Clone Cells; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Immunobiology; Ionomycin - pharmacology; Lymphocyte Activation - drug effects; Mice; Mice, Inbred C57BL; Organs and cells involved in the immune response; Ovalbumin - immunology; Proto-Oncogene Proteins c-myc - genetics; Receptor Aggregation; Receptors, Cell Surface - metabolism; Receptors, Transforming Growth Factor beta; RNA, Messenger - genetics; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transforming Growth Factor beta - pharmacology; Tumor Necrosis Factor-alpha - pharmacology; Cell cloning; Transforming growth factor; Rodentia; Helper cell; Gene expression; Cell subpopulation; Northern blotting; Resistance; Vertebrata; Membrane receptor; Sensitivity; Mammalia; Mouse; T-Lymphocyte
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.146.9.3063

Three ovalbumin-specific T helper cell lines (OVA-7T cells) that differ in their susceptibility to the immunosuppressive effects of transforming growth factor-beta (TGF-beta) were cloned. The frequency of TGF-beta-resistant OVA-7T cell clones correlated with the decline of TGF-beta sensitivity in the original OVA-7T parental cell lines. In TGF-beta-resistant OVA-7T cell clones, TGF-beta inhibited neither the growth of the T cells nor their secretion of granulocyte macrophage CSF. TGF-beta suppressed the expression of c-myc mRNA in OVA-7T-responder but not in OVA-7T-nonresponder cells. TGF-beta resistance was found to be due to a loss of TGF-beta high-affinity binding sites, with an absence of expression of the distinct 54-, 70-, 110-, and 250-kDa surface proteins that bind TGF-beta on TGF-beta-susceptible T cells. Loss of TGF-beta R may enable T cells to escape the negative feedback control provided by TGF-beta secreted from activated T cells during an immune response.