Membrane gangliosides modulate interleukin-2-stimulated T-lymphocyte proliferation.
Membrane gangliosides appear to modulate signal transduction by several growth factor receptors. We have investigated the possible regulation of IL-2-induced proliferation signals by gangliosides. Low concentrations of cholera toxin B subunit (CT-B), which binds specifically to GM1 ganglioside, greatly inhibited IL-2-stimulated DNA synthesis in the IL-2-dependent cell line CTLL-2, but had no effect on proliferation of HT-2. GM1 levels proved to be very low in HT-2 compared to CTLL-2. Large increases in membrane-associated GM1 could be achieved in both cell lines by incubation with exogenous GM1, resulting in a high degree of inhibition of proliferation by CT-B for both CTLL-2 and HT-2. Inhibition was blocked by large unilamellar vesicles containing GM1, but not by vesicles of lipid alone. The time course of CT-B inhibition for CTLL-2 synchronized in G0-G1, indicated that the negative growth signal acts relatively early in the IL-2 activation pathway. CT-B did not affect binding of IL-2 to high-affinity IL-2r. The inhibitory effects of CT-B could not be reversed by pertussis toxin, suggesting that a G protein is probably not involved. These results show that CT-B binding to either endogenous or inserted GM1 can modulate IL-2-induced lymphocyte proliferation.
Sharom
F J
FJ
Guelph-Waterloo Centre for Graduate Work in Chemistry, University of Guelph, Ontario, Canada.
Chiu
A L
AL
Chu
J W
JW
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D004357:Drug Synergism; D005677:G(M1) Ganglioside / Q000032:analysis / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D008051:Lipid Bilayers / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis / Q000494:pharmacology*; D051379:Mice; D037342:Pertussis Toxin; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006131:Growth Inhibitors; D007376:Interleukin-2; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010566:Virulence Factors, Bordetella; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D037342:Pertussis Toxin