Cameron S B, Nawijn M C, Kum W W, Savelkoul H F, Chow A W
Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver Hospital, Vancouver, B.C., Canada.
Eur Cytokine Netw. 2001 Apr-Jun;12(2):210-22.
Staphylococcal superantigens (sAgs) including toxic shock syndrome toxin-1 (TSST-1) and related enterotoxins are exoproteins with unique immunobiological properties. They bind to major histocompatibility complex (MHC) class II molecules of antigen-presenting cells outside the peptide groove, and induce massive proliferation of T cells bearing specific V beta determinants. This tri-molecular interaction leads to uncontrolled release of various proinflammatory cytokines especially interferon-gamma (IFN-gamma) and tumor necrosis factor-a (TNF-alpha), the key cytokines causing sAg-mediated shock. The effector T cells involved in this hyper-immune response are predominantly of the T helper-1 (Th1) phenotype. There is also some evidence that polarization to a Th2 response with the production of classical anti-inflammatory cytokines (such as interleukins IL-4 and IL-6) also occurs. Moreover, the emergence of a novel regulatory T cell (Tr1) subset, producing mainly IL-10 but little or no IL-2 and IL-4, has recently been described following repeated sAg stimulation. In this review, the current knowledge regarding the regulation of T helper cell subsets in response to staphylococcal sAgs is critically evaluated, and the role of various cytokines which directly influence T cell differentiation and polarization is summarized. Particular emphasis is directed towards pro-inflammatory as well as anti-inflammatory and regulatory effector functions during toxic shock. Based on this review, we propose that a delayed production of IL-10 by Tr1 cells may be the most prominent driving force in the down-regulation of the Th1 hyper-immune response, and the critical determinant for the eventual recovery of the host.
包括中毒性休克综合征毒素-1（TSST-1）及相关肠毒素在内的葡萄球菌超抗原（sAgs）是具有独特免疫生物学特性的外毒素。它们在肽槽外侧与抗原呈递细胞的主要组织相容性复合体（MHC）II类分子结合，并诱导带有特定Vβ决定簇的T细胞大量增殖。这种三分子相互作用导致各种促炎细胞因子尤其是干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）不受控制地释放，这些关键细胞因子会引发sAg介导的休克。参与这种超免疫反应的效应T细胞主要为T辅助细胞1（Th1）表型。也有一些证据表明，还会出现向产生经典抗炎细胞因子（如白细胞介素IL-4和IL-6）的Th2反应极化的情况。此外，最近有报道称，在反复的sAg刺激后会出现一个新的调节性T细胞（Tr1）亚群，该亚群主要产生IL-10，但很少或不产生IL-2和IL-4。在这篇综述中，对目前关于T辅助细胞亚群对葡萄球菌sAgs反应的调节的认识进行了批判性评估，并总结了直接影响T细胞分化和极化的各种细胞因子的作用。特别强调了中毒性休克期间的促炎以及抗炎和调节效应功能。基于这篇综述，我们提出Tr1细胞延迟产生IL-10可能是Th1超免疫反应下调的最主要驱动力，也是宿主最终恢复的关键决定因素。
