Schiffenbauer J, Johnson H M, Butfiloski E J, Wegrzyn L, Soos J M
Department of Medicine, University of Florida, Gainesville 32610.
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8543-6. doi: 10.1073/pnas.90.18.8543.
Staphylococcal enterotoxins (SEs) are one member of a unique group of molecules known as superantigens. They are potent T-cell activators and stimulate a large number of T cells bearing specific T-cell-receptor beta-chain variable regions. It has been proposed that superantigens may trigger autoimmune disorders by stimulation of autoreactive T cells with restricted beta-chain variable-chain usage. We investigated the effects of SEs B and A (SEB and SEA) on the reactivation of experimental allergic encephalomyelitis, an animal model for multiple sclerosis. We report that SEB can reinduce encephalitis multiple times in PL/J mice that had previously recovered from an acute episode. SEB was also able to induce encephalitis in mice previously immunized with myelin basic protein but did not show clinical signs of disease. In addition, it was observed that T cells from PL/J mice that had been previously activated by myelin basic protein in complete Freund's adjuvant or in complete Freund's adjuvant alone were resistant to the induction of anergy by SEB. To determine whether reactivation of experimental allergic encephalomyelitis was specific for SEB, another superantigen, SEA, was employed. It was found that SEA was also able to reinduce experimental allergic encephalomyelitis in mice previously recovered from an acute episode and those that had been previously immunized with myelin basic protein but did not show clinical signs of disease. These results indicate that SEs are capable of reactivating autoreactive T cells and inducing autoimmune disease.
葡萄球菌肠毒素(SEs)是一类独特分子(称为超抗原)中的一员。它们是强效的T细胞激活剂,能刺激大量带有特定T细胞受体β链可变区的T细胞。有人提出,超抗原可能通过刺激使用受限的β链可变链的自身反应性T细胞来引发自身免疫性疾病。我们研究了SEs B和A(SEB和SEA)对实验性变应性脑脊髓炎(一种多发性硬化症的动物模型)再激活的影响。我们报告称,SEB能在先前已从急性发作中恢复的PL/J小鼠中多次重新诱发脑炎。SEB还能够在先前用髓鞘碱性蛋白免疫但未表现出疾病临床症状的小鼠中诱发脑炎。此外,观察到,先前在完全弗氏佐剂中或仅在完全弗氏佐剂中被髓鞘碱性蛋白激活的PL/J小鼠的T细胞对SEB诱导的无反应性具有抗性。为了确定实验性变应性脑脊髓炎的重新激活是否对SEB具有特异性,使用了另一种超抗原SEA。结果发现,SEA也能够在先前已从急性发作中恢复的小鼠以及先前用髓鞘碱性蛋白免疫但未表现出疾病临床症状的小鼠中重新诱发实验性变应性脑脊髓炎。这些结果表明,SEs能够重新激活自身反应性T细胞并诱发自身免疫性疾病。