Skov M, Poulsen L K, Koch C
Danish Cystic Fibrosis Center, Department of Pediatrics, National University Hospital, Copenhagen.
Pediatr Pulmonol. 1999 Feb;27(2):74-9. doi: 10.1002/(sici)1099-0496(199902)27:2<74::aid-ppul2>3.0.co;2-l.
The majority of patients with cystic fibrosis (CF) become colonized with Aspergillus fumigatus (A. fumigatus) in the lower respiratory tract, the prevalence being up to 60%. Between 1-11% of CF patients develop allergic bronchopulmonary aspergillosis (ABPA). Previous studies of ABPA in selected patients suffering from cystic fibrosis or atopic asthma have suggested a pathogenic role for antigen-specific "Th2-like" T lymphocytes. The aim of this study was to evaluate the quantitative importance of such Th2 cells, using improved techniques for measuring interleukin-4 (IL-4) and IL-5 secretion in unseparated peripheral blood mononuclear cell (PBMC) suspensions from CF patients with ABPA and from a control group without ABPA. Thus, 20 patients with CF, heavily colonized with A. fumigatus in the lower respiratory tract, were studied: 10 patients with ABPA, and 10 without. Unseparated PBMC were stimulated in vitro by A. fumigatus antigen and by an unrelated antigen (tetanus toxoid) as a control. After 6 days of stimulation, IL-4 and IL-5 (markers for Th2 cell activity) and interferon-gamma (IFN-gamma) (marker for Th1 cell activity) were quantified in the supernatants by enzyme-linked immunosorbent assay. PBMC from ABPA patients secreted significantly higher amounts of IL-4, i.e., 0.48 (0.15-0.8) ng/mL (median (range)), and IL-5, 37.64 (0.32-82.85) ng/mL, compared to secretions obtained in non-ABPA CF controls of 0.07 (0.04-0.16) ng/mL and 3.00 (0.10-5.09) ng/mL, respectively (P < 0.01 for both). IFN-gamma secretion was similar in the two groups, amounting to 21.5 (2.05-72.5) ng/mL in ABPA patients vs. 20.75 (1.80-54.0) ng/mL in non-ABPA patients (P = 0.47). No significant differences were obtained in the cytokine secretion induced by tetanus toxoid stimulation between the two groups. We conclude that ABPA in CF patients is associated with an antigen-specific, Th2-like T-cell immune response, as indicated by excessive secretion of IL-4 and IL-5.
大多数囊性纤维化（CF）患者的下呼吸道会被烟曲霉（A. fumigatus）定植，其患病率高达60%。1%至11%的CF患者会发展为变应性支气管肺曲霉病（ABPA）。先前针对患有囊性纤维化或特应性哮喘的特定患者进行的ABPA研究表明，抗原特异性“Th2样”T淋巴细胞具有致病作用。本研究的目的是使用改进的技术，测量来自患有ABPA的CF患者和无ABPA的对照组的未分离外周血单个核细胞（PBMC）悬液中白细胞介素-4（IL-4）和IL-5的分泌情况，以评估此类Th2细胞在数量上的重要性。因此，研究了20名下呼吸道被烟曲霉严重定植的CF患者：10名患有ABPA，10名未患ABPA。未分离的PBMC在体外分别受到烟曲霉抗原和一种无关抗原（破伤风类毒素）刺激作为对照。刺激6天后，通过酶联免疫吸附测定法对外上清液中的IL-4和IL-5（Th2细胞活性标志物）以及干扰素-γ（IFN-γ，Th1细胞活性标志物）进行定量。与未患ABPA的CF对照组相比，ABPA患者的PBMC分泌的IL-4显著更高，即0.48（0.15 - 0.8）ng/mL（中位数（范围）），IL-5为37.64（0.32 - 82.85）ng/mL，而未患ABPA的CF对照组分别为0.07（0.04 - 0.16）ng/mL和3.00（0.10 - 5.09）ng/mL（两者P均<0.01）。两组的IFN-γ分泌相似，ABPA患者为21.5（2.05 - 72.5）ng/mL，未患ABPA的患者为20.75（1.80 - 54.0）ng/mL（P = 0.47）。两组之间破伤风类毒素刺激诱导的细胞因子分泌无显著差异。我们得出结论，CF患者中的ABPA与抗原特异性的Th2样T细胞免疫反应相关，这表现为IL-4和IL-5的过度分泌。
