Till S, Dickason R, Huston D, Humbert M, Robinson D, Larché M, Durham S, Kay A B, Corrigan C
Allergy and Clinical Immunology Section, National Heart and Lung Institute, Imperial College of Science Technology and Medicine, London, United Kingdom.
J Allergy Clin Immunol. 1997 Apr;99(4):563-9. doi: 10.1016/s0091-6749(97)70085-x.
IL-5-producing allergen-specific T cells are thought to play a prominent role in the pathogenesis of allergic inflammation. We hypothesized that T cell allergen-driven IL-5 synthesis is elevated in patients with atopic disease as compared with that in atopic patients free of disease and nonatopic control subjects.
The purpose of this study was to compare IL-5 and interferon-gamma (IFN-gamma) secretion and proliferation by peripheral blood T cells from sensitized atopic patients with asthma, rhinitis, and no symptoms and from nonatopic control subjects in response to the allergen Dermatophagoides pteronyssinus (Der p) and the control recall antigen Mycobacterium tuberculosis purified protein derivative (PPD).
To measure allergen-induced IL-5 production and proliferation, we developed a short-term culture technique that required a single antigenic stimulation of freshly isolated peripheral blood mononuclear cells (PBMC). With this technique, we measured Der p- and PPD-induced IL-5 production and proliferation in PBMC from atopic patients with asthma who were allergic to Der p, atopic patients with rhinitis, atopic patients with no symptoms, and a group of nonatopic normal control subjects. In four experiments, CD4+ or CD8+ T cells were depleted from PBMC to confirm that IL-5 synthesis was T cell dependent.
T cell IL-5 production, but not IFN-gamma production, in response to Der p was elevated in atopic patients with asthma and atopic patients with rhinitis compared with findings in atopic patients with no symptoms or nonatopic control subjects. IL-5 production was abrogated by depletion of CD4+, but not CD8+, T cells. In subjects with asthma, allergen-driven IL-5 production correlated with bronchial hyperreactivity. Allergen-induced proliferation was also higher in patients with asthma than in atopic subjects with no symptoms or nonatopic controls. T cell IL-5 and IFN-gamma production and proliferation in response to PPD were similar regardless of atopic status or disease.
Elevated IL-5 production is a characteristic of allergen-specific peripheral blood CD4+ T cells from sensitized patients with atopic disease but not atopy per se.
产生白细胞介素-5(IL-5)的变应原特异性T细胞被认为在过敏性炎症的发病机制中起重要作用。我们假设,与无疾病的特应性患者和非特应性对照受试者相比,特应性疾病患者中T细胞变应原驱动的IL-5合成升高。
本研究的目的是比较来自患有哮喘、鼻炎且无症状的致敏特应性患者以及非特应性对照受试者的外周血T细胞对变应原屋尘螨(Der p)和对照回忆抗原结核分枝杆菌纯化蛋白衍生物(PPD)的IL-5和干扰素-γ(IFN-γ)分泌及增殖情况。
为了测量变应原诱导的IL-5产生和增殖,我们开发了一种短期培养技术,该技术需要对新鲜分离的外周血单个核细胞(PBMC)进行单次抗原刺激。利用该技术,我们测量了对Der p过敏的哮喘特应性患者、鼻炎特应性患者、无症状特应性患者以及一组非特应性正常对照受试者的PBMC中Der p和PPD诱导的IL-5产生和增殖。在四项实验中,从PBMC中去除CD4+或CD8+ T细胞以确认IL-5合成是T细胞依赖性的。
与无症状特应性患者或非特应性对照受试者相比,哮喘特应性患者和鼻炎特应性患者对Der p反应的T细胞IL-5产生增加,但IFN-γ产生未增加。去除CD4+ T细胞可消除IL-5产生,但去除CD8+ T细胞则不会。在哮喘患者中,变应原驱动的IL-5产生与支气管高反应性相关。哮喘患者中变应原诱导的增殖也高于无症状特应性受试者或非特应性对照。无论特应状态或疾病如何,T细胞对PPD反应的IL-5和IFN-γ产生及增殖情况相似。
IL-5产生增加是致敏特应性疾病患者而非特应性本身的变应原特异性外周血CD4+ T细胞的特征。