Transforming growth factor-beta (TGF-beta)-resistant helper T lymphocyte clones show a concomitant loss of all three types of TGF-beta receptors.
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.
Siepl
C
C
Section of Clinical Immunology, University Hospital, Zürich, Switzerland.
Malipiero
U V
UV
Fontana
A
A
D000818:Animals; D015152:Blotting, Northern; D002999:Clone Cells; D015870:Gene Expression; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011940:Receptor Aggregation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D010047:Ovalbumin; D013755:Tetradecanoylphorbol Acetate