Burastero S E, Crimi E, Balbo A, Vavassori M, Borgonovo B, Gaffi D, Frittoli E, Casorati G, Rossi G A
Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan, Italy.
J Immunol. 1995 Dec 15;155(12):5836-46.
We were interested in studying the lung allergen-specific T cell repertoire in different conditions of allergen exposure in subjects with atopic asthma. Twenty-one allergic individuals were studied: 17 subjects suffering mainly from asthma and 4 from rhinitis. They all performed spirometry and methacholine challenge. All patients were subjected to bronchoalveolar lavage (BAL), either at base line (no challenge) or after allergen or histamine challenge, and the TCR repertoire of their lung T cells was studied with heteroduplex analysis. Expansion of single T cell clones was observed in one (of seven) asthmatic subject that reported a recent exposure to allergen and had high bronchial hypersensitivity to methacholine, and in seven/seven asthmatic subjects who underwent BAL after they suffered an early asthmatic reaction to experimental allergen inhalation. Remarkably, ex vivo expanded clones included allergen-specific T cells. In two of the seven subjects who underwent BAL after allergen challenge, two different lung segments were lavaged. A strikingly symmetrical distribution of the expanded clones was found in these samples. Control subjects and six of seven asthmatic patients studied at base line showed polyclonality of lung T cells. In conclusion, T lymphocytes are clonally expanded in the lower respiratory tract only in asthmatic subjects exposed to allergen. These results suggest that in allergic asthma, the inhalation of sensitizing allergens can recruit to the lung T lymphocytes that include allergen-specific T cell clones.
我们感兴趣的是研究特应性哮喘患者在不同变应原暴露条件下的肺变应原特异性T细胞库。研究了21名过敏个体:17名主要患有哮喘,4名患有鼻炎。他们都进行了肺功能测定和乙酰甲胆碱激发试验。所有患者在基线(无激发)时或变应原或组胺激发后接受支气管肺泡灌洗(BAL),并采用异源双链分析研究其肺T细胞的TCR库。在一名(共7名)报告近期接触过变应原且对乙酰甲胆碱有高支气管高反应性的哮喘患者中,以及在7名/7名在吸入实验性变应原后出现早期哮喘反应后接受BAL的哮喘患者中,观察到单个T细胞克隆的扩增。值得注意的是,体外扩增的克隆包括变应原特异性T细胞。在变应原激发后接受BAL的7名受试者中的2名中,对两个不同的肺段进行了灌洗。在这些样本中发现扩增克隆呈现出惊人的对称分布。对照受试者和7名哮喘患者中的6名在基线时研究显示肺T细胞呈多克隆性。总之,仅在接触变应原的哮喘患者的下呼吸道中T淋巴细胞发生克隆性扩增。这些结果表明,在过敏性哮喘中,吸入致敏变应原可将包括变应原特异性T细胞克隆的T淋巴细胞募集到肺中。