Superantigen modulation of experimental allergic encephalomyelitis: activation of anergy determines outcome.
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced by the adoptive transfer of CD4, myelin basic protein (MBP)-specific T cells. Superantigens activate T cells expressing appropriate TCR V genes. In this study, MBP-specific T cells activated in vitro with a superantigen, staphylococcal enterotoxin B (SEB), could adoptively transfer a severe form of EAE in (PLxSJL)F1 mice, but did not transfer disease in PL/J or SJL/J mice. SEB treatment of donor mice anergized MBP-specific T cells using V beta 8 in (PLxSJL)F1 mice, because subsequent in vitro activation with SEB resulted in a marked decrease in proliferation to SEB and inability to transfer EAE. However, donor cells from (PLxSJL)F1 mice immunized with MBP/CFA that had been exposed to SEB in vivo before MBP stimulation in vitro still produced EAE in recipient mice. To confirm that non-V beta 8 T cells could transfer disease, donor mice were treated with antibody that eliminated V beta 8 T cells; MBP-activated T cells from these mice could still transfer EAE. Finally, EAE induced by SEB-activated T cells was substantially reduced in mice receiving anti-V beta 8 therapy in vivo. The ability of superantigens to activate encephalitogenic T cells may have relevance to human diseases such as multiple sclerosis.
Racke
M K
MK
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Quigley
L
L
Cannella
B
B
Raine
C S
CS
McFarlin
D E
DE
Scott
D E
DE
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology; D017634:Self Tolerance; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000637:transplantation
D004768:Enterotoxins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal