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首页> 外文期刊>Infection and immunity >The Pseudomonas aeruginosa Quorum-Sensing Molecule N-3-(Oxododecanoyl)-l-Homoserine Lactone Inhibits T-Cell Differentiation and Cytokine Production by a Mechanism Involving an Early Step in T-Cell Activation
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The Pseudomonas aeruginosa Quorum-Sensing Molecule N-3-(Oxododecanoyl)-l-Homoserine Lactone Inhibits T-Cell Differentiation and Cytokine Production by a Mechanism Involving an Early Step in T-Cell Activation

机译：铜绿假单胞菌群体感应分子N-3-（氧十二烷酰基）-1-高丝氨酸内酯通过涉及T细胞活化早期步骤的机制抑制T细胞分化和细胞因子产生。

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The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-l-homoserine lactone (OdDHL) has been reported to have immunomodulatory activity in several systems, although the mechanism of that activity remains to be fully characterized. We demonstrate here, using a defined in vitro model of antigen responses by T-cell receptor (TCR)-transgenic mouse splenic CD4 T cells, that the effect of OdDHL on activation and cytokine production is complete within 4 h of antigen or mitogen stimulation and does not depend on the insertion of OdDHL in the cell membrane, despite a previous report that immunosuppression by homoserine lactones required a minimum acyl chain length of 11 carbons (S. R. Chhabra, C. Harty, D. S. W. Hooi, M. Daykin, B. W. Bycroft, P. Williams, and D. Pritchard, J. Med. Chem. >46:97-104, 2003). We also demonstrate that while OdDHL can have toxic effects on nonlymphoid leukocytes, it does not induce significant cell death in T cells at the concentrations (≤10 μM) used in these experiments. In addition, we show that primary and secondary antigen-specific cytokine responses are equally susceptible to inhibition by OdDHL and that the compound inhibits the differentiation of both Th1 and Th2 cells. However, the precise balance of cytokine production by CD4 T cells stimulated in the presence of OdDHL varies with both the antigen concentration and its affinity for the transgenic TCR. Thus, conflicting reports of the nature of the immunosuppression by OdDHL may be due in part to the differences in antigen affinity and concentration in different models.
机译：据报道，铜绿假单胞菌群体感应分子 N -3-（氧十二烷酰基）-1-高丝氨酸内酯（OdDHL）在几个系统中具有免疫调节活性，尽管其机制该活动的特征有待充分表征。我们在这里使用已定义的体外T细胞受体（TCR）转基因小鼠脾CD4 T细胞抗原反应模型证明，OdDHL对激活和细胞因子产生的影响在抗原或促分裂原刺激的4小时内完成，并且尽管以前有报道称高丝氨酸内酯的免疫抑制作用要求酰基链的最小长度为11个碳原子（SR Chhabra，C.Harty，DSW Hooi，M.Daykin，BW Bycroft，P），但它并不依赖于OdDHL在细胞膜中的插入。 Williams和D. Pritchard，J。Med。Chem。> 46： 97-104，2003）。我们还证明，尽管OdDHL可以对非淋巴白细胞产生毒性作用，但在这些实验中使用的浓度（≤10μM）下，它不会在T细胞中诱导明显的细胞死亡。此外，我们显示一级和二级抗原特异性细胞因子反应同样容易受到OdDHL的抑制，并且该化合物抑制Th1和Th2细胞的分化。但是，在OdDHL存在下刺激的CD4 T细胞产生的细胞因子的精确平衡随抗原浓度及其对转基因TCR的亲和力而变化。因此，有关OdDHL免疫抑制性质的报道相互矛盾，可能部分是由于不同模型中抗原亲和力和浓度的差异所致。

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