Till S J, Durham S R, Rajakulasingam K, Humbert M, Huston D, Dickason R, Kay A B, Corrigan C J
Imperial College School of Medicine, National Heart and Lung Institute, Charing Cross and Royal Brompton Campuses, London, United Kingdom.
Am J Respir Crit Care Med. 1998 Aug;158(2):404-11. doi: 10.1164/ajrccm.158.2.9705007.
In order to detect and characterize allergen-specific T cells in the airways of atopic asthmatics, we measured proliferation and cytokine production by bronchoalveolar lavage (BAL) T cells isolated from Dermatophagoides pteronyssinus (Der p)-sensitive asthmatics and nonatopic control subjects, and compared the results with those generated using peripheral blood (PB) T cells. BAL and PB mononuclear cells were collected 24 h after segmental allergen challenge by fibreoptic bronchoscopy and venepuncture, respectively. T cells purified from BAL and PB were stimulated with autologous, irradiated antigen-presenting cells and D. pteronyssinus extract or a control, nonallergen antigen (M. tuberculosis purified protein derivative [PPD]). IL-5 and IFN-gamma concentrations were measured in culture supernatants by ELISA, and T-cell proliferation by 3H-thymidine uptake. D. pteronyssinus-induced proliferation of T cells derived from both BAL and PB was elevated in asthmatics when compared with control subjects (p < 0.05), whereas PPD-induced proliferation was equivalent in both compartments. In the asthmatics, D. pteronyssinus-induced proliferative responses of equivalent numbers of BAL and PB T cells obtained after allergen challenge were statistically equivalent. Nevertheless, BAL T cells stimulated with D. pteronyssinus produced significantly greater amounts of IL-5 than did PB T cells (p < 0.05). Allergen-induced proliferation and IL-5 production by BAL T cells in the asthmatics after segmental allergen challenge correlated with the percentages of eosinophils in the BAL fluid (p < 0.01). Further, BAL T cells from asthmatic patients produced significantly higher amounts of IL-5 than did the same number of cells from nonatopic control subjects (p < 0.05). We conclude that, in D. pteronyssinus-sensitive asthmatics, allergen-specific T cells can be detected in the bronchial lumen after allergen challenge and that allergen-induced proliferation and IL-5 production by these cells correlates with local eosinophil influx. Although bronchial luminal T cells show an equivalent proliferative response to allergen stimulation as compared with PB T cells, they do produce more IL-5, consistent with the hypothesis that local differentiation or priming of these cells within the bronchial mucosal environment results in upregulation of allergen-induced IL-5 secretion.
为了检测和鉴定特应性哮喘患者气道中过敏原特异性T细胞，我们测量了从对屋尘螨（Der p）敏感的哮喘患者和非特应性对照受试者分离的支气管肺泡灌洗（BAL）T细胞的增殖和细胞因子产生情况，并将结果与外周血（PB）T细胞的结果进行比较。分别在通过纤维支气管镜和静脉穿刺进行节段性过敏原激发24小时后收集BAL和PB单核细胞。从BAL和PB中纯化的T细胞用自体照射的抗原呈递细胞和屋尘螨提取物或对照非过敏原抗原（结核分枝杆菌纯化蛋白衍生物[PPD]）刺激。通过ELISA测量培养上清液中的IL-5和IFN-γ浓度，并通过3H-胸苷摄取测量T细胞增殖。与对照受试者相比，屋尘螨诱导的来自BAL和PB的T细胞增殖在哮喘患者中升高（p <0.05），而PPD诱导的增殖在两个区室中相当。在哮喘患者中，过敏原激发后获得的等量BAL和PB T细胞的屋尘螨诱导的增殖反应在统计学上相当。然而，用屋尘螨刺激的BAL T细胞产生的IL-5量明显高于PB T细胞（p <0.05）。节段性过敏原激发后哮喘患者BAL T细胞的过敏原诱导的增殖和IL-5产生与BAL液中嗜酸性粒细胞的百分比相关（p <0.01）。此外，哮喘患者的BAL T细胞产生的IL-5量明显高于相同数量的非特应性对照受试者的细胞（p <0.05）。我们得出结论，在对屋尘螨敏感的哮喘患者中，过敏原激发后可在支气管腔内检测到过敏原特异性T细胞，并认为这些细胞的过敏原诱导的增殖和IL-5产生与局部嗜酸性粒细胞流入相关。尽管支气管腔内T细胞与PB T细胞相比对过敏原刺激表现出相当的增殖反应，但它们确实产生更多的IL-5，这与以下假设一致：这些细胞在支气管黏膜环境中的局部分化或启动导致过敏原诱导的IL-5分泌上调。
