Expression of mucosa-related integrin α(E)β7 on alveolar T cells in interstitial lung diseases

Abstract

The expression of α(E)β7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated α(E)β7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD), α(E) 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 α(E)-bearing T cells in peripheral blood was <2%, whereas the vast majority of alveolar CD8+ T cells consistently coexpressed α(E). Absolute alveolar CD8+α(E)+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of α(E)- 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 α(E) 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 α(E) expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express α(E)β7 and that distinct patterns of α(E)β7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung.