Inhibition of CD8+ T Lymphocytes Attenuates Respiratory Syncytial Virus-Enhanced Allergic Inflammation

Abstract

Background: CD8+ T cells have an important role in the pathogenesis of respiratory virus-induced asthma exacerbations. However, the cellular mechanism of CD8+ T cells, linking viral respiratory infections to the development of airway inflammation, is not well defined. Objectives: To clarify the role of CD8+ T cells in the development of respiratory virus-induced asthma exacerbations. Methods: Using a murine model of prior ovalbumin exposure and subsequent respiratory syncytial virus infection, the airway responsiveness was assessed by barometric whole-body plethysmography. Airway eosinophils, lymphocytes, neutrophils as well as IFN-γ, IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were measured by Diff-Quick staining and ELISA. The frequency of cytokine-producing CD8+ T lymphocytes in peribronchial lymph nodes was detected using 2-color immunofluorescence analysis. Histological examinations were carried out using hematoxylin and eosin and immunohistochemistry. Results: Anti-CD8 monoclonal antibody (1 mg/kg) clearly inhibited increases in airway responsiveness to acetylcholine and markedly reduced the number of eosinophils, neutrophils, lymphocytes as well as IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid. Furthermore, the antibody also attenuated airway inflammation and CD8+ T lymphocyte infiltration in lung tissue. Conclusions: These findings suggest that CD8+ T lymphocytes play a critical role for the development of respiratory syncytial virus-induced airway inflammation and airway hyperresponsiveness.