T Lymphocytes and Eosinophils in Allergen-induced Late-phase Asthmatic Reactions in the Guinea Pig

Abstract
The kinetics and phenotype of T lymphocytes infiltrating the airways of guinea pigs undergoing late-phase asthmatic reactions (LAR) were studied with monoclonal antibodies, cytofluorimetry, and immunocytochemistry. Challenge of sensitized animals with aerosolized ovalbumin was followed by early (2 h) and late-phase (17 h) bronchoconstriction. The induction of hypersensitivity, by aerosolized antigen, was associated with an increase in mucosal T cell numbers, which consisted almost entirely of CD8+ T cells. Following allergen challenge of fully sensitized animals, a biphasic rise in total T cell (CD3+) numbers was observed in the bronchial mucosa, peaking at 17 and 48 h. A similar pattern of T cell accumulation was observed in the bronchial adventitia but with an extra early peak at 2 h. In contrast to the T cell influx of the sensitization phase, the postchallenge infiltrate consisted largely of CD3 + ,CD8− cells. Eosinophil numbers were elevated in both submucosa and adventitia, with a single broad peak between 17 and 48 h. T cell infiltration was compared with eosinophil accumulation: while correlations between T cell and eosinophil numbers varied over the 96 h of the experiment, strong associations were observed between CD8+ numbers and eosinophils in the adventitia at 6 h (r = 0.733, p < 0.01) and between CD3+ numbers and eosinophils in the submucosa at 72 h (r = 0.88, p < 0.001). No significant changes were detected in T cell or eosinophil numbers in the lung parenchyma. There was a postchallenge increase in eosinophils (but not T cells) in bronchoalveolar lavage (BAL). In contrast, analysis of blood leukocytes showed no changes in T cell total or subset numbers during the progression of the LAR. These results indicate that accumulation of T cells in the airways is a feature of the LAR in this model. These observations are consistent with human BAL and skin studies of the allergen-induced late-phase reaction. These data also illustrate that evaluation of distant compartments (blood and BAL) may not fully reflect rapidly evolving tissue infiltration in the bronchial mucosa.

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