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ZAP70 expression in regulatory T cells in allergic rhinitis: Effect of immunotherapy

机译：ZAP70在变应性鼻炎中调节性T细胞中的表达：免疫疗法的影响

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Background: Some allergic diseases may be accompanied by inappropriate number or malfunction of regulatory T cells, which seems to be modified by specific immunotherapy (SIT). Objectives: To assess if immunotherapy affects regulatory T lymphocytes (Tregs) and their expression of zeta chain associated protein kinase (Zap70), which is essential for T cell activation and intracellular signal downstream transduction. Methods: A 3-year prospective, placebo-controlled, double-blind trial of grass SIT was conducted. Forty-one patients sensitized to grass pollen with intermittent allergic rhinitis were randomized to receive SIT (n = 21) or placebo (n = 20) and 15 healthy were included as a control. Concentration of exhaled nitric oxide (ENO), lung function, symptom scores, the subsets of regulatory T cells (CD4+ CD25hiCD127low) which express ZAP70 and the level of ZAP70 expression in this subset were assessed at baseline and during the treatment period: before the onset, at the height of the pollen season and after the end of the pollen season. Results: The concentration of nitric oxide and the symptom score were significantly higher in allergic rhinitis patients as compared with the control group. Natural allergen stimulation diminished both the numbers of regulatory T cells that express ZAP70 and the expression of Zap70 within these cells. In the second year of treatment, immunotherapy reduced significantly the symptom scores, concentrations of ENO (P 0.01), intensively increased expression of ZAP70 in regulatory T cells (P 0.001) and the percentage of cells that express ZAP70 (P 0.05) at the height of the pollen season. Placebo treatment did not reduce scores, ENO (P 0.05) nor had influence on Zap70 expression (P 0.05). Conclusions: SIT with grass pollen effectively reduces rhinitis severity and affects allergic airway inflammation reflected by reduction of ENO. Beneficial role of immunotherapy may result not only from the induction of Treg numbers but especially from cell activation and restitution of Treg intracellular signal transduction.
机译：背景：某些过敏性疾病可能伴有调节性T细胞数量不正确或功能异常，这似乎可以通过特异性免疫疗法（SIT）加以改善。目的：评估免疫疗法是否会影响调节性T淋巴细胞（Tregs）及其Zeta链相关蛋白激酶（Zap70）的表达，这对于T细胞活化和细胞内信号下游转导至关重要。方法：进行了一项为期3年的前瞻性安慰剂对照双盲试验。将对花粉过敏，间歇性变应性鼻炎致敏的41例患者随机接受SIT（n = 21）或安慰剂（n = 20），以15名健康人作为对照。在基线和治疗期间：发病前评估呼出气一氧化氮（ENO）浓度，肺功能，症状评分，表达ZAP70的调节性T细胞亚群（CD4 + CD25hiCD127low）和ZAP70表达水平。 ，在花粉旺季和花粉旺季结束后。结果：变应性鼻炎患者的一氧化氮浓度和症状评分均明显高于对照组。自然的过敏原刺激减少了表达ZAP70的调节性T细胞的数量以及这些细胞内Zap70的表达。在治疗的第二年，免疫疗法显着降低了症状评分，ENO浓度（P <0.01），在调节性T细胞中ZAP70的表达大量增加（P <0.001）和表达ZAP70的细胞百分比（P <0.05）在花粉旺季。安慰剂治疗未降低评分，ENO（P> 0.05），也未影响Zap70表达（P> 0.05）。结论：SIT与草花粉可有效降低鼻炎的严重程度，并通过减少ENO反映过敏性气道炎症。免疫疗法的有益作用不仅可以归因于Treg数目的诱导，而且尤其可以归因于Treg细胞内信号转导的细胞活化和恢复。

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