Nakata A, Kaminuma O, Ogawa K, Fujimura H, Fushimi K, Kikkawa H, Naito K, Ikezawa K, Egan R W, Mori A
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
Int Immunol. 2001 Mar;13(3):329-39. doi: 10.1093/intimm/13.3.329.
The relationship between CD4(+) T cell-mediated airway eosinophilic inflammation and bronchial hyper-responsiveness (BHR) was investigated. Ovalbumin-reactive T(h)0 clones were adoptively transferred to unprimed BALB/c mice and then the mice were challenged by inhalation of the relevant antigen. Upon antigen provocation, infused T(h) clones infiltrated into the airways, followed by the accumulation and degranulation of eosinophils, goblet cell hyperplasia, edema and increase in bronchial responsiveness to acetylcholine. Transfer of several clones that differed in the levels of IL-5 production revealed that the magnitude of in vivo eosinophilia strongly correlated with the IL-5-producing capacity of the infused T(h) clones. Administration of anti-IL-5 mAb almost completely suppressed antigen-induced eosinophilic inflammation and BHR. Administration of anti-IL-4 mAb or anti-IFN-gamma mAb enhanced the eosinophilia and BHR, whereas anti-IL-2 mAb did not affect them. The number of accumulated eosinophils significantly correlated with the intensity of BHR. Our present results clearly demonstrated that CD4(+) T cells induced BHR as a result of eosinophilic inflammation. IL-5 totally regulated both responses.
研究了CD4(+) T细胞介导的气道嗜酸性粒细胞炎症与支气管高反应性（BHR）之间的关系。将卵清蛋白反应性T(h)0克隆过继转移至未致敏的BALB/c小鼠，然后通过吸入相关抗原对小鼠进行激发。抗原激发后，注入的T(h)克隆浸润至气道，随后嗜酸性粒细胞聚集和脱颗粒、杯状细胞增生、水肿以及支气管对乙酰胆碱的反应性增加。转移几个IL-5产生水平不同的克隆显示，体内嗜酸性粒细胞增多的程度与注入的T(h)克隆产生IL-5的能力密切相关。给予抗IL-5单克隆抗体几乎完全抑制了抗原诱导的嗜酸性粒细胞炎症和BHR。给予抗IL-4单克隆抗体或抗IFN-γ单克隆抗体增强了嗜酸性粒细胞增多和BHR，而抗IL-2单克隆抗体对其无影响。聚集的嗜酸性粒细胞数量与BHR的强度显著相关。我们目前的结果清楚地表明，CD4(+) T细胞由于嗜酸性粒细胞炎症而诱导了BHR。IL-5完全调节了这两种反应。
