Abe J, Forrester J, Nakahara T, Lafferty J A, Kotzin B L, Leung D Y
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicines, Denver, CO 80206.
J Immunol. 1991 Jun 1;146(11):3747-50.
Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.
链球菌外毒素与中毒性休克样综合征和猩红热的发病机制有关。先前的研究表明,这些毒素是人类T细胞的强效刺激剂,并且与葡萄球菌肠毒素具有结构同源性。在本研究中,我们调查了A组(SPEA)和B组链球菌致热外毒素(SPEB)激活T细胞的机制,并将其与抗CD3和已知的“超抗原”葡萄球菌肠毒素B进行比较。结果发现,SPEA选择性激活携带Vβ8、Vβ12和Vβ14的T细胞,而SPEB选择性激活携带Vβ2和Vβ8的T细胞。此外,转染了II类主要组织相容性复合体分子的成纤维细胞能够将SPEA和SPEB呈递给纯化的T细胞。然而,T细胞对这些毒素的反应不受主要组织相容性复合体限制。虽然链球菌外毒素刺激CD4+和CD8+ T细胞,但SPEA而非SPEB对CD4+ T细胞亚群的刺激比对CD8+ T细胞亚群的刺激更为显著。我们的结果表明,SPEA和SPEB与葡萄球菌肠毒素一样,都是超抗原,并提示了它们可能介导与链球菌感染相关的特定全身综合征的机制。