Gangliosides inhibit phenotypic and functional properties of an encephalitogenic T-helper lymphocyte line.
Gangliosides were evaluated for their ability to inhibit the phenotype and function of an encephalitogenic T-helper lymphocyte line from Lewis rats (BP-1), which responds specifically to guinea pig myelin basic protein (GP-BP). After activation for 3 days with GP-BP, the BP-1 line induced a lethal form of experimental autoimmune encephalomyelitis (EAE) in recipient rats 3-6 days after intraperitoneal injection. Incubation of activated BP-1 line cells with 250 microM gangliosides for 1 hr prior to injection prevented EAE completely in 5/14 recipients and markedly reduced the severity of clinical signs and histologic lesions in the rest. Similar treatment of BP-1 cells with galactocerebroside had no inhibitory effect. Both individual and mixed gangliosides inhibited accessory cell-dependent activation of BP-1 cells with GP-BP. Gangliosides also inhibited BP-1 activation with a cell-free supernatant containing accessory cell-processed GP-BP and rat Ia molecules, suggesting that the inhibition was not restricted to accessory cell function. In addition to inhibiting antigen-dependent proliferation, gangliosides inhibited IL-2 dependent cell growth. Furthermore, individual and mixed gangliosides blocked binding of anti-T-helper cell antibody (W3/25) to the BP-1 line, while galactocerebroside, ceramide, and sialic acid had no inhibitory effect. Cell surface staining of T-total, T-non-helper, or Ia determinants was relatively unaffected by gangliosides. Taken together, the immunomodulatory properties of gangliosides on T-effector cell function lend biologic importance to the increased levels of gangliosides which have been reported in human diseases with immunoregulatory abnormalities such as multiple sclerosis, rheumatoid arthritis, and cancer.
Offner
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Vandenbark
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D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005732:Gangliosides / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007376:Interleukin-2; D004676:Myelin Basic Protein