Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen.
The role of infection in the pathogenesis of clinical relapses that occur in most autoimmune diseases, including multiple sclerosis, remains to be established. Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis, with episodes of relapsing paralysis. In certain strains of mice, T-lymphocytes expressing the V beta 8 T-cell receptor (TCR) engage the amino-terminal epitope Ac1-11 of myelin basic protein, leading to EAE. The bacterial superantigen staphylococcal enterotoxin B (SEB) activates V beta 8-expressing T cells. Here we show that after immunization with Ac1-11, or after transfer of encephalitogenic T-cell lines or clones reactive to Ac1-11, SEB induces exacerbation or relapses of paralytic disease in mice that are in clinical remission following an initial episode of paralysis, and triggers paralysis in mice with subclinical disease. Tumour necrosis factor has a critical role in the mechanism underlying SEB-induced exacerbation of disease, because anti-tumour necrosis factor antibody given in vivo delays the onset of paralysis triggered by SEB. On reactivation of autoaggressive cells through their T-cell receptor, superantigens may induce clinical relapses of autoimmune disease.
Brocke
S
S
Department of Neurology, Stanford University School of Medicine, California 94305.
Gaur
A
A
Piercy
C
C
Gautam
A
A
Gijbels
K
K
Fathman
C G
CG
Steinman
L
L
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010243:Paralysis / Q000276:immunology* / Q000503:physiopathology; D013211:Staphylococcus aureus; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004768:Enterotoxins; D004676:Myelin Basic Protein; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal