Crisi G M, Santambrogio L, Hochwald G M, Smith S R, Carlino J A, Thorbecke G J
Department of Pathology, New York University School of Medicine, New York, USA.
Eur J Immunol. 1995 Nov;25(11):3035-40. doi: 10.1002/eji.1830251108.
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)-alpha (0.2 micrograms, 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 V beta 17a+T cells are still partially deleted. In these mice, however, TNF-alpha is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)-beta and TNF-alpha have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF-beta and anti-TNF were protective, while anti-TGF-beta caused disease exacerbation. Interleukin (IL)-10 is also known to counteract certain TNF effects. We now find that both human IL-10 and TGF-beta 2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF-alpha. The protective effect of TGF-beta 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-beta 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-beta production appears to limit the susceptibility to induction of EAE relapses in this model.
对超抗原葡萄球菌肠毒素B（SEB）诱导已从急性实验性自身免疫性脑脊髓炎（EAE）部分或完全恢复的SJL小鼠发生EAE复发的能力进行了研究。我们发现静脉注射0.05mg SEB单次注射可使50%的此类小鼠发生轻度复发。此外，在恢复后1 - 2个月腹腔注射肿瘤坏死因子（TNF）-α（0.2μg）也可使43%的SJL小鼠发生EAE复发。当Vβ17a + T细胞仍部分缺失时再次注射SEB不会诱导第二次复发。然而，在这些小鼠中，TNF-α诱导复发的效果与未预先接受SEB的小鼠相同。我们之前表明转化生长因子（TGF）-β和TNF-α对实验性自身免疫性疾病具有拮抗作用；例如，在自发复发性EAE中，TGF-β和抗TNF具有保护作用，而抗TGF-β会导致疾病加重。白细胞介素（IL）-10也已知可抵消某些TNF的作用。我们现在发现，人IL-10和TGF-β2与SEB或TNF-α同时给予时，均可降低EAE复发的发生率。TGF-β的保护作用仅对SEB诱导的复发有显著效果（降至9%），而IL-10的保护作用仅对TNF诱导的复发有效果（降至0%），采用的治疗方案如此。中和性抗TGF-β不会增加SEB诱导的EAE复发的发生率。相反，抗IL-10会增加此类复发的发生率和严重程度。我们得出结论，TNF的产生可能在导致EAE复发中起重要作用，但SEB诱导的髓鞘特异性T细胞重新激活的其他方面也有作用。此外，在该模型中，内源性IL-10而非TGF-β的产生似乎限制了对EAE复发诱导的易感性。
