ACCELERATED INDUCTION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN PL J MICE BY A NON-V(BETA)8-SPECIFIC SUPERANTIGEN/

Superantigens such as the staphylococcal enterotoxins can play an impo rtant role in exacerbation of autoimmune disorders such as experimenta l allergic encephalomyelitis (EAE) in mice. In fact, superantigens can reactivate EAE in PL/J mice that have been sensitized to rat myelin b asic protein (MBP). The T-cell subset predominantly responsible for di sease in PL/J mice bears the V(beta)8(+) T-cell antigen receptor (TCR) , The question arises as to whether T cells bearing other V-beta speci ficities are involved in induction or reactivation of EAE with superan tigen, Thus, we have investigated the ability of a non-V(beta)8-specif ic superantigen, staphylococcal enterotoxin A (SEA) (V-beta specificit ies 1, 3, 10, 11, and 17), to induce EAE in PL/J mice that have been p reviously protected from disease by anergy and deletion of V(beta)8(+) T cells, PL/J mice were first pretreated with the V(beta)8-specific s uperantigen staphylococcal enterotoxin B (SEB) and then immunized with MBP, These mice exhibited V(beta)8-specific anergy and depletion and did not develop EAE, even when further treated with SEB. However, admi nistration of SEA to these same mice induced an initial episode of EAE which was characterized by severe hindleg paralysis and accelerated o nset of disease, In contrast to SEB pretreatment, PL/J mice pretreated with SEA did develop EAE when immunized with MBP, and after resolutio n of clinical signs of disease these mice were susceptible to relapse of EAE induced by SEE but not by SEA, Thus, superantigens can activate encephalitogenic MBP-specific non-V(beta)8(+) T cells to cause EAE in PL/J mice, These data suggest that superantigens can play a central r ole in autoimmune disorders and that they introduce a profound complex ity to autoimmune diseases such as EAE, akin to the complexity seen in multiple sclerosis.