INDUCTION OF RELAPSING PARALYSIS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY BACTERIAL SUPERANTIGEN

THE role of infection in the pathogenesis of clinical relapses that oc cur in most autoimmune diseases, including multiple sclerosis, remains to be established1,2. Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis, with episodes of relapsing paralysis3-9. In certain strains of mice, T-lymphocytes expressing the Vbeta8 T-cell receptor (TCR)6-8 engage the amino-terminal epitope Ac1 -11 of myelin basic protein, leading to EAE. The bacterial superantige n staphylococcal enterotoxin B (SEB) activates Vbeta8-expressing T cel ls. Here we show that after immunization with Ac1-11, or after transfe r of encephalitogenic T-cell lines or clones reactive to Ac1-11, SEB i nduces exacerbation or relapses of paralytic disease in mice that are in clinical remission following an initial episode of paralysis, and t riggers paralysis in mice with subclinical disease. Tumour necrosis fa ctor has a critical role in the mechanism underlying SEB-induced exace rbation of disease, because anti-tumour necrosis factor antibody given in vivo delays the onset of paralysis triggered by SEB. On reactivati on of autoaggressive cells through their T-cell receptor, superantigen s may induce clinical relapses of autoimmune disease.