Center for Vaccine Development, University of Maryland School of Medicine, Baltimore MD 21201, USA.
Clin Immunol. 2013 Feb;146(2):140-52. doi: 10.1016/j.clim.2012.12.003. Epub 2012 Dec 20.
Toxic shock syndrome (TSS) is a potentially life threatening condition characterized by fever, rash, shock, and multi-organ failure. Staphylococcal enterotoxin B (SEB) is a well characterized superantigen that has been shown to play an important role in TSS. Although the precise mechanisms by which SEB and other superantigens cause TSS are unknown, induction of a pro-inflammatory cytokine cascade appears central to this phenomenon. We show that CD4+ and CD8+ Teffector/memory (T(EM)) and other subsets produce IL-17A following SEB stimulation. We also show that IL-17A is co-produced with other pro-inflammatory cytokines (i.e., IL-2, IFN-γ and TNF-α). These responses are significantly different than those elicited by mitogenic stimulation. Multifunctional IL-17A producing cells possess markers typical of the T(H)17/T(C)17 and T(H)1 subsets, including CCR6, IL-22, and transcription factors retinoic acid receptor-related orphan nuclear receptor (ROR)-γt and T-bet. These results suggest a possible role for IL-17A-producing multifunctional T cells in the pathogenesis of TSS.
中毒性休克综合征(TSS)是一种潜在的危及生命的病症,其特征是发热、皮疹、休克和多器官衰竭。葡萄球菌肠毒素 B(SEB)是一种特征明确的超抗原,已被证明在 TSS 中起重要作用。尽管 SEB 和其他超抗原导致 TSS的确切机制尚不清楚,但诱导促炎细胞因子级联反应似乎是这种现象的核心。我们表明,SEB 刺激后 CD4+和 CD8+效应器/记忆(T(EM))和其他亚群会产生 IL-17A。我们还表明,IL-17A 与其他促炎细胞因子(即 IL-2、IFN-γ 和 TNF-α)共同产生。这些反应与有丝分裂刺激引起的反应明显不同。多功能的产生 IL-17A 的细胞具有 T(H)17/T(C)17 和 T(H)1 亚群的典型标记物,包括 CCR6、IL-22 和转录因子维甲酸受体相关孤儿核受体(ROR)-γt 和 T-bet。这些结果表明,产生 IL-17A 的多功能 T 细胞可能在 TSS 的发病机制中起作用。