Temporal sequence and kinetics of proinflammatory and anti-inflammatory cytokine secretion induced by toxic shock syndrome toxin 1 in human peripheral blood mononuclear cells
Temporal sequence and kinetics of proinflammatory and anti-inflammatory cytokine secretion induced by toxic shock syndrome toxin 1 in human peripheral blood mononuclear cells
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DOI：
10.1128/iai.69.12.7544-7549.2001
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发表时间：
2001-12-01
影响因子：
3.1
通讯作者：
Chow, AW
中科院分区：
文献类型：
--
作者：
Kum, WWS;Cameron, SB;Chow, AW
葡萄球菌超抗原中毒性休克综合征毒素1（TSST-1）诱导大量细胞因子产生，被认为是TSS发病的关键因素。研究了TSST-1在人外周血单个核细胞中诱导的促炎和抗炎细胞因子的时间顺序和动力学。一组TSST-1的功能丧失的单氨基酸取代突变体，先前被证明在主要组织相容性复合体（MHC）II类结合（G31 R）或T细胞受体（TCR）相互作用（H135 A，S14 N）中存在缺陷，进行了平行研究，以进一步阐明细胞因子分泌的机制。野生型重组（WT r）TSST-1诱导细胞因子分泌的双相模式：早期快速释放促炎细胞因子（特别是γ干扰素，白细胞介素-2 [IL-2]和肿瘤坏死因子α [TNF-α]），以及更晚的阶段，促炎性细胞因子和细胞因子的产生更缓慢。在刺激后16至72小时内检测IL-1 β、IL-12和TNF-β和IL-6、IL-10细胞因子。G31 R，这是在MHC II类结合缺陷，诱导类似于WT rTSST-1的细胞因子谱，除了早期促炎细胞因子的分泌延迟和IL-1 β和IL-12的产生显着减少。相比之下，TCR相互作用缺陷的突变型毒素在整个观察期内表现出完全不存在任何细胞因子分泌（H135 A）或导致IL-2和其他早期促炎细胞因子的完全消除，而IL-10的分泌似乎不受影响（S14 N）。WT rTSST-1和突变毒素均未诱导IL-4或转化生长因子β。我们的数据表明，有效的TCR相互作用是诱导早期促炎细胞因子反应的关键，从而强调了T细胞信号转导在TSS中的重要性。
The staphylococcal superantigen toxic shock syndrome toxin 1 (TSST-1) induces massive cytokine production, which is believed to be the key factor in the pathogenesis of TSS. The temporal sequence and kinetics of both proinflammatory and anti-inflammatory cytokines induced by TSST-1 in human peripheral blood mononuclear cells were investigated. A panel of loss-of-function single-amino-acid-substitution mutants of TSST-1, previously demonstrated to be defective in either major histocompatibility complex (MHC) class II binding (G31R) or T-cell receptor (TCR) interaction (H135A, S14N), was studied in parallel to further elucidate the mechanisms of cytokine secretion. Wild-type recombinant (WT r) TSST-1 induced a biphasic pattern of cytokine secretion: an early phase with rapid release of proinflammatory cytokines (especially gamma interferon, interleukin-2 [IL-2], and tumor necrosis factor alpha [TNF-alpha]) within 3 to 4 h poststimulation, and a later phase with more gradual production of both proinflammatory (IL-1 beta, IL-12, and TNF-beta) and antiinflammatory (IL-6, IL-10) cytokines within 16 to 72 h poststimulation. G31R, which is defective in MHC class II binding, induced a cytokine profile similar to that of WT rTSST-1, except that secretion of the early-phase proinflammatory cytokines was delayed and production of IL-1 beta and IL-12 was markedly reduced. In contrast, mutant toxins defective in TCR interaction either demonstrated complete absence of any cytokine secretion during the entire observation period (H135A) or resulted in complete abolishment of IL-2 and other early-phase proinflammatory cytokines, while secretion of IL-10 appeared unaffected (S14N). Neither WT rTSST-1 nor the mutant toxins induced IL-4 or transforming growth factor beta. Our data indicate that effective TCR interaction is critical for the induction of the early-phase proinflammatory cytokine response, thus underscoring the importance of T-cell signaling in TSS.