de Jong E C, Spanhaak S, Martens B P, Kapsenberg M L, Penninks A H, Wierenga E A
Netherlands Organization for Applied Scientific Research, Nutrition and Food Research Institute, Zeist.
J Allergy Clin Immunol. 1996 Jul;98(1):73-81. doi: 10.1016/s0091-6749(96)70228-2.
Increasing evidence indicates a prominent role of allergen-specific TH2 cells, with high IL-4 and IL-5 production and low interferon-gamma production, in the regulation of IgE and eosinophil production in allergic disorders. However, most studies have concentrated on T cells reactive with inhalation allergens, whereas little is known about the properties of food allergen-reactive T cells.
In this study we therefore characterized peanut-specific T cells, cloned from a patient with severe peanut allergy.
Peripheral blood mononuclear cells from patients with peanut allergy and nonallergic individuals were stimulated with crude peanut extract (CPE) to compare the proliferative responses and to select a suitable patient for the cloning of CPE-specific T cells. The resultant panel of CPE-reactive T-lymphocyte clones was serologically phenotyped by flow cytometry and analyzed for cytokine secretion by ELISA.
The patients' peripheral blood mononuclear cells showed a dose-dependent proliferation response to CPE, which was significantly higher (p < 0.05) than in peripheral blood mononuclear cells of nonallergic donors. The CPE-specific T-lymphocyte clones generated from the selected patient were all CD4+/CD8- T helper cells with a TH2 cytokine profile, secreting high amounts of IL-4 and IL-5, but little or no interferon-gamma.
This study demonstrates that peanut-specific T cells do occur in the peripheral blood of patients with peanut allergy and suggests an increased frequency of these T cells in patients compared with nonallergic control subjects. The CD4+ phenotype and the TH2 cytokine profile of the CPE-specific T-lymphocyte clones suggest a functional role of allergen-specific TH2 cells in the pathophysiology of food allergy, similar to the function of inhalation allergen-specific TH2 cells.
越来越多的证据表明,在过敏性疾病中,产生高白细胞介素-4和白细胞介素-5且低干扰素-γ的变应原特异性TH2细胞在调节IgE和嗜酸性粒细胞生成方面发挥着重要作用。然而,大多数研究集中于与吸入性变应原反应的T细胞,而对于食物变应原反应性T细胞的特性了解甚少。
因此,在本研究中,我们对从一名严重花生过敏患者克隆出的花生特异性T细胞进行了特性分析。
用粗制花生提取物(CPE)刺激花生过敏患者和非过敏个体的外周血单个核细胞,以比较增殖反应,并选择合适的患者用于克隆CPE特异性T细胞。通过流式细胞术对所得的CPE反应性T淋巴细胞克隆进行血清学表型分析,并通过酶联免疫吸附测定法分析细胞因子分泌情况。
患者的外周血单个核细胞对CPE呈剂量依赖性增殖反应,该反应显著高于非过敏供者的外周血单个核细胞(p<0.05)。从选定患者产生的CPE特异性T淋巴细胞克隆均为CD4+/CD8-T辅助细胞,具有TH2细胞因子谱,分泌大量白细胞介素-4和白细胞介素-5,但几乎不分泌或不分泌干扰素-γ。
本研究表明,花生特异性T细胞确实存在于花生过敏患者的外周血中,提示与非过敏对照受试者相比,这些T细胞在患者中的频率增加。CPE特异性T淋巴细胞克隆的CD4+表型和TH2细胞因子谱表明,变应原特异性TH2细胞在食物过敏的病理生理学中发挥功能作用,类似于吸入性变应原特异性TH2细胞的功能。