Multi-sialo brain gangliosides are powerful stimulators of active E-rosetting lymphocytes from multiple sclerosis patients

Peripheral blood T lymphocytes from all of 14 patients with clinically definite multiple sclerosis (MS) were significantly stimulated by MS brain gangliosides in the active rosetting of sheep erythrocytes. Fractionated mono- and disialogangliosides were devoid of any stimulating effect on MS lymphocytes whereas the trisialoganglioside G_T1 and to a greater extent the tetrasialoganglioside G_Q1b were fully effective at a dose as low as 2 × 10^-18 moles. Gangliosides extracted from MS brains or from MS brain myelin were far more effective than gangliosides derived from control human brains or from bovine and mouse brains, suggesting the importance of highly sialylated gangliosides occurring to a greater extent in MS brain as previously reported. Lymphocytes from only 3 out of 24 other neurological patients were stimulated by the slow migrating gangliosides in the same way, but none of 32 healthy subjects responded to these gangliosides in the active E-rosette test. Lymphocytes from 5 of 8 patients with unilateral optic neuritis reacted positively to brain gangliosides by rosette formation, several weeks before a similar reaction to myelin basic protein was evident. Our data are compatible with a release of gangliosides during demyelination or other CNS degenerative processes occurring in multiple sclerosis.