Division of Immunology and Allergy, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
J Immunol Res. 2015;2015:384780. doi: 10.1155/2015/384780. Epub 2015 Mar 31.
In order to determine the potential for allergen to modulate T cell expression of the CysLT1 receptor and responsiveness to leukotrienes, peripheral blood mononuclear cells from house dust mite-allergic or nonallergic individuals were incubated with D. pteronyssinus allergen (Der p). Baseline CysLT1 expression was similar in both groups of donors, but Der p significantly enhanced CysLT1 expression in CD4(+) and CD8(+) T cells of only allergic individuals and induced enhanced responsiveness of CD4(+) T cells to LTD4 in terms of calcium mobilisation. This effect was prevented by the CysLT1 antagonist MK571. Der p also induced IL-4 and IL-10 production, and neutralizing antibody to IL-4 prevented both the enhanced CysLT1 expression and the enhanced responsiveness of T cells to LTD4 induced by Der p. In allergic individuals, Der p also induced T cell proliferation and a Th2-biased phenotype. Our data suggest that, in allergen-sensitized individuals, exposure to allergen can enhance T cell expression of CysLT1 receptors through a mechanism involving IL-4 production. This, in turn, would induce CD4(+) T cell responsiveness to cysteinyl-leukotrienes and Th2 cell activation.
为了确定过敏原是否能够调节 T 细胞表达 CysLT1 受体和对白细胞三烯的反应性，我们从尘螨过敏或非过敏个体的外周血单核细胞中孵育 D. pteronyssinus 过敏原（Der p）。在这两组供体中，基础 CysLT1 表达相似，但 Der p 仅在过敏个体的 CD4(+)和 CD8(+)T 细胞中显著增强 CysLT1 表达，并诱导 CD4(+)T 细胞对 LTD4 的钙动员反应增强。这种效应被 CysLT1 拮抗剂 MK571 所阻断。Der p 还诱导了 IL-4 和 IL-10 的产生，而抗 IL-4 的中和抗体可预防 Der p 诱导的 CysLT1 表达增强和 T 细胞对 LTD4 的反应性增强。在过敏个体中，Der p 还诱导了 T 细胞增殖和 Th2 偏向表型。我们的数据表明，在过敏原致敏个体中，暴露于过敏原可通过涉及 IL-4 产生的机制增强 T 细胞表达 CysLT1 受体。这反过来又会诱导 CD4(+)T 细胞对半胱氨酰白三烯的反应性和 Th2 细胞的激活。
