SUPERANTIGEN MODULATION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - ACTIVATION OR ANERGY DETERMINES OUTCOME

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced by the adoptive transfer of CD4, myelin basic pro tein (MBP)-specific T cells. Superantigens activate T cells expressing appropriate TCR V genes. In this study, MBP-specific T cells activate d in vitro with a superantigen, staphylococcal enterotoxin B (SEB), co uld adoptively transfer a severe form of EAE in (PLxSJL)F1 mice, but d id 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. Howeve r, donor cells from (PLxSJL)F1 mice immunized with MBP/CFA that had be en exposed to SEB in vivo before MBP stimulation in vitro still produc ed EAE in recipient mice. To confirm that non-V beta 8 T cells could t ransfer disease, donor mice were treated with antibody that eliminated V beta 8 T cells; MBP-activated T cells from these mice could still t ransfer EAE. Finally, EAE induced by SEB-activated T cells was substan tially reduced in mice receiving anti-V beta 8 therapy in vivo. The ab ility of superantigens to activate encephalitogenic T cells may have r elevance to human diseases such as multiple sclerosis.