Laaksonen Kirsi, Junikka Miia, Lahesmaa Riitta, Terho Erkki O, Savolainen Johannes
Department of Pulmonary Disease and Clinical Allergology, University of Turku, Turku, Finland.
J Allergy Clin Immunol. 2003 Dec;112(6):1171-7. doi: 10.1016/j.jaci.2003.08.043.
Specific immunotherapy (SIT) acts by inducing a shift from T(H)2 to T(H)1 cell response on mucous membranes, reducing allergic inflammation. New genes expressed primarily in T(H)1-type cells have been found. Of these genes, signaling lymphocytic activation molecule (SLAM) promotes T-cell proliferation and IFN-gamma production. Nothing is known about its role in T(H)2-T(H)1 switch during SIT.
We sought to analyze the mRNA expression of SLAM and other T(H)1-associated genes, interleukin-12 receptor beta2 (IL-12Rbeta2) and T-box expressed in T cells (T-bet), and compare them with the clinical outcome of the therapy.
PBMC from 30 patients allergic to pollen undergoing SIT were collected during the therapy. Control PBMC were collected from 10 patients with allergic rhinitis not participating in SIT and from 10 nonallergic subjects. Cells were stimulated in vitro with pollen allergen extracts. SLAM, IL-12Rbeta2, and T-bet mRNA expressions were studied by real-time quantitative RT-PCR technique (Taqman). Symptom scoring and medication scoring were registered before commencement of SIT and after 1 year of the therapy.
Before the treatment, in vitro allergen-induced SLAM mRNA expression in PBMC was significantly lower in the patients with allergic rhinitis than in the healthy control subjects. After 1 year of the treatment, SLAM mRNA expression was increased in the patients undergoing SIT and was associated with IFN-gamma mRNA expression and inversely associated with the symptom improvement. At the maintenance dose, an increase in SLAM mRNA expression was associated with the clinical symptom improvement at 1 year. No changes were seen in IL-12Rbeta(2) or T-bet mRNA expressions.
SLAM mRNA expression in PBMC is modulated during the course of SIT, and an early and transient increase of SLAM mRNA expression is associated with clinical symptom improvement.
特异性免疫疗法(SIT)通过诱导黏膜上从辅助性T细胞2(TH2)向辅助性T细胞1(TH1)细胞反应的转变来发挥作用,从而减轻变应性炎症。已发现主要在TH1型细胞中表达的新基因。在这些基因中,信号淋巴细胞激活分子(SLAM)可促进T细胞增殖和γ干扰素的产生。关于其在SIT期间TH2向TH1转换中的作用尚不清楚。
我们试图分析SLAM以及其他与TH1相关基因白细胞介素12受体β2(IL-12Rβ2)和T细胞表达的T盒(T-bet)的mRNA表达,并将它们与治疗的临床结果进行比较。
在治疗期间收集30例对花粉过敏且正在接受SIT的患者的外周血单个核细胞(PBMC)。对照PBMC取自10例未参与SIT的变应性鼻炎患者和10例非变应性受试者。用花粉变应原提取物在体外刺激细胞。通过实时定量逆转录-聚合酶链反应技术(Taqman)研究SLAM、IL-12Rβ2和T-bet mRNA的表达。在SIT开始前和治疗1年后记录症状评分和用药评分。
治疗前,变应性鼻炎患者PBMC中体外变应原诱导的SLAM mRNA表达明显低于健康对照受试者。治疗1年后,接受SIT的患者SLAM mRNA表达增加,且与γ干扰素mRNA表达相关,与症状改善呈负相关。在维持剂量时,SLAM mRNA表达增加与1年后临床症状改善相关。IL-12Rβ2或T-bet mRNA表达未见变化。
PBMC中SLAM mRNA表达在SIT过程中受到调节,SLAM mRNA表达的早期短暂增加与临床症状改善相关。