Staphylococcal enterotoxin B and tumor-necrosis factor-α-induced relapses of experimental allergic encephalomyelitis: Protection by transforming growth factor-β and interleukin-10

A study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. induces mild relapses in 50% of such mice. In addition, tumor necrosis factor (TNF)-α (0.2 μg, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1–2 months after recovery. SEB does not induce a second relapse if reinjected when Vβ17a+ T cells are still partially deleted. In these mice, however, TNF-α is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)-β and TNF-α have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF-β and anti-TNF were protective, while anti-TGF-β caused disease exacerbation. Interleukin (IL)-10 is also known to counteract certain TNF effects. We now find that both human IL-10 and TGF-β2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF-α. The protective effect of TGF-β is significant only against relapses induced by SEB (reduced to 9%), and that of IL-10 only against relapses induced by TNF (reduced to 0%) with the treatment regimens employed. Neutralizing anti-TGF-β does not increase the incidence of SEB-induced EAE relapses. In contrast, anti-IL-10 increases both the incidence and the severity of such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB-induced reactivation of myelin-specific T cells also contribute. Furthermore, endogenous IL-10 rather than TGF-β production appears to limit the susceptibility to induction of EAE relapses in this model.