Oligoclonality of lung T lymphocytes following exposure to allergen in asthma.

Abstract

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.