Gavett S H, Chen X, Finkelman F, Wills-Karp M
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Am J Respir Cell Mol Biol. 1994 Jun;10(6):587-93. doi: 10.1165/ajrcmb.10.6.8003337.
The pathogenesis of asthma remains unclear. An in vivo murine model of antigen-induced airway hyperreactivity and inflammation was developed to investigate the possibility, suggested by a wealth of descriptive human data, that alterations in immunoregulation are important in the genesis of airway hyperreactivity. A/J mice developed airway hyperreactivity and markedly increased numbers of pulmonary inflammatory cells following intraperitoneal sensitization and intratracheal challenge with sheep red blood cells. Notably, eosinophils were a prominent component of the inflammatory infiltrate. The dependence of these phenomena, both pathologic and functional, on CD4+ T lymphocytes was investigated by in vivo depletion of CD4+ cells using the anti-CD4 mAb GK1.5. When administered before antigen challenge, GK1.5 completely prevented both airway hyperreactivity and the infiltration of eosinophils. This model provides the first direct demonstration of the dependence of airway hyperreactivity upon CD4+ T lymphocytes, and the results are consistent with the possibility that eosinophils are effectors of this response.
哮喘的发病机制仍不清楚。为了研究免疫调节改变在气道高反应性发生过程中是否重要（这一可能性由大量描述性人体数据所提示），构建了一种抗原诱导的气道高反应性和炎症的体内小鼠模型。用绵羊红细胞对A/J小鼠进行腹腔致敏和气管内激发后，小鼠出现气道高反应性，肺部炎性细胞数量显著增加。值得注意的是，嗜酸性粒细胞是炎性浸润的主要成分。通过使用抗CD4单克隆抗体GK1.5在体内耗竭CD4+细胞，研究了这些病理和功能现象对CD4+ T淋巴细胞的依赖性。在抗原激发前给予GK1.5，可完全预防气道高反应性和嗜酸性粒细胞浸润。该模型首次直接证明了气道高反应性对CD4+ T淋巴细胞的依赖性，结果与嗜酸性粒细胞是这种反应的效应细胞这一可能性相一致。
