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.
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Offner
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Vandenbark
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