Krug N, Madden J, Redington A E, Lackie P, Djukanovic R, Schauer U, Holgate S T, Frew A J, Howarth P H
Immunopharmacology Group, Southampton, United Kingdom.
Am J Respir Cell Mol Biol. 1996 Apr;14(4):319-26. doi: 10.1165/ajrcmb.14.4.8600935.
Atopic asthma is characterized by bronchial mucosal inflammation, involving eosinophils, mast cells, and lymphocytes. It has been suggested that the development and maintenance of this allergic inflammation is due to T-lymphocyte activation with predominant production of the cytokines interleukin 4 (IL-4) and IL-5. To address the ability of peripheral blood and bronchoalveolar lavage T-cells to generate IL-2, IL-4, or interferon gamma (IFN-gamma), we have employed a flow cytometric method which permits analysis of cytokine production at the single cell level within 5 h of obtaining cell samples. When stimulated with PMA and ionomycin, there was a greatly increased percentage of IFN-gamma-producing cells among bronchoalveolar lavage (BAL) T-cells from the subjects with asthma (median 74%), compared with atopic and nonatopic controls (35 and 43%, respectively; P>0.01). The proportion of BAL T-cells producing IL-4 was small (median 1.7%, range 0 to 7.8% in the asthmatic group). In all three groups, the proportion of BAL T-cells producing IL-2 or IFN-gamma was increased compared with T-cells from peripheral blood. There was no significant difference between the three groups in the percentage of BAL T-cells producing IL-2, or in the percentage of peripheral blood T-cells producing IFN-gamma, IL-2 or IL-4. These findings indicate that IL-4 production is confined to a relatively small proportion of airway and blood T-cells and that there is selective enhancement of IFN-gamma production by airway T-cells in asthma.
特应性哮喘的特征是支气管黏膜炎症,涉及嗜酸性粒细胞、肥大细胞和淋巴细胞。有人提出,这种过敏性炎症的发生和维持是由于T淋巴细胞活化,主要产生细胞因子白细胞介素4(IL-4)和IL-5。为了研究外周血和支气管肺泡灌洗T细胞产生IL-2、IL-4或干扰素γ(IFN-γ)的能力,我们采用了一种流式细胞术方法,该方法能够在获取细胞样本后5小时内对单细胞水平的细胞因子产生情况进行分析。用佛波酯(PMA)和离子霉素刺激后,哮喘患者支气管肺泡灌洗(BAL)T细胞中产生IFN-γ的细胞百分比大幅增加(中位数为74%),相比之下,特应性和非特应性对照分别为35%和43%(P>0.01)。产生IL-4的BAL T细胞比例较小(哮喘组中位数为1.7%,范围为0至7.8%)。在所有三组中,与外周血T细胞相比,产生IL-2或IFN-γ的BAL T细胞比例增加。三组之间产生IL-2的BAL T细胞百分比,或外周血T细胞产生IFN-γ、IL-2或IL-4的百分比均无显著差异。这些发现表明,IL-4的产生仅限于气道和血液中相对较小比例的T细胞,并且哮喘患者气道T细胞中IFN-γ的产生有选择性增强。