Expression of mucosa-related integrin αEβ7 on alveolar T cells in interstitial lung diseases

Abstract

SUMMARY The expression of αEβ7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated αEβ7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD),αE expression on CD4+ and CD8+ T cell subsets was evaluated by dual-colour flow cytometry in peripheral blood and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF; n = 18), hypersensitivity pneumonitis (HP; n = 20) and sarcoidosis (n = 44) in comparison with healthy controls (n = 15). In both healthy individuals and all patient groups the proportion of αE-bearing T cells in peripheral blood was < 2%, whereas the vast majority of alveolar CD8+ T cells consistently co-expressed αE. Absolute alveolar CD8+αE+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of αE-bearing CD4+ cells in BALF were significantly elevated in IPF (74.0 ± 2.7%) and HP (70.0 ±  2.4%) compared with normals (30.0 ± 1.8%) (mean ±  s.e.m.; P < 0.01). In sarcoidosis, the αE expression on BALF CD4+ cells displayed subgroup dependency: proportions significantly lower than normal were noted in chest radiographic stage I (14.3 ± 1.5%), but increased proportions in stages II (50.0 ± 3.8%) and III (64.0 ± 4.8%). Correlations between common markers of T cell activation or BALF transforming growth factor-beta (TGF-β) bioactivity and αE expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express αEβ7 and that distinct patterns of αEβ7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung.