PROTECTION FROM EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY APPLICATION OF A BACTERIAL SUPERANTIGEN

Certain bacterial and viral T cell stimulating proteins ('superantigens') are known to be very potent activators of T cells with certain V(beta) receptors. When applied in vivo these molecules induce anergy in those T cells responding to them. In this study we have investigated the influence of staphylococcal enterotoxins (SE) on myelin basic protein (MBP)-specific T cells in Lewis rats. As MBP-specific T cells in rats belong exclusively to the V(beta)8.2+ CD4+ subset, the induction of experimental allergic encephalomyelitis (EAE) allows for an estimation of the functional state of the respective V(beta)-bearing T cells after enterotoxin-induced activation. In vitro, various MBP-specific T cell lines showed a strong selective proliferative response to staphylococcal enterotoxin E (SEE) but not to other SE. The in vitro activation by SEE induced encephalitogenic potential in these cells. After application of SEE to Lewis rats the susceptibility to induction of EAE was completely abrogated. Such SEE-treated and MBP-challenged rats did not exhibit any signs of disease and their T cells did not respond to MBP in proliferation tests. This abrogation of EAE was only found with a superantigen capable of interacting specifically with V(beta)8.2+ T cells. Superantigen-mediated induction of unresponsiveness may have relevance for the analysis of pathogenetic mechanisms and for therapeutic considerations in certain T cell-mediated autoimmune diseases.