Activation of CD4+ T cells, increased T H2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma

Abstract

Background: We have examined whether the local eosinophilia provoked by inhalational allergen challenge of patients with atopic asthma is associated with the appearance, in vivo, of activated T H2-type T helper lymphocytes. Methods: Fifteen patients with atopic asthma had bronchial wash and bronchoalveolar lavage (BAL) 24 hours after allergen or diluent challenge separated by at least 21 days. Results: There was an increase in eosinophils in both bronchial wash ( p = 0.01) and BAL ( p = 0.02) after allergen challenge but not after diluent challenge. Activation of CD4+ BAL T cells was suggested by an increase in the expression of CD25 shown by flow cytometry after allergen challenge, when compared with diluent ( p = 0.02). There was no evidence of activation of CD8 T cells. By in situ hybridization after allergen challenge as compared with diluent, increases were shown in the numbers of cells expressing mRNA for interleukin-4 (IL-4) ( p = 0.005), IL-5 ( p = 0.01), and granulocyte-macrophage colony-stimulating factor ( p = 0.03) but not IL-3, IL-2, or interferon-γ. In situ hybridization of BAL cells after immunomagnetic separation of CD2-positive and CD2-negative cell populations showed that IL-4 and IL-5 mRNAs were associated with T lymphocytes after allergen challenge. BAL and bronchial wash eosinophilia closely correlated with maximal late fall in forced expiratory volume in 1 second after allergen challenge. Conclusion: Cytokines produced by activated T H2-type CD4+ T cells in the airway may contribute to late asthmatic responses by mechanisms that include eosinophil accumulation.