T Cells Are Necessary for Th 2 Cytokine Production and Eosinophil Accumulation in Airways of Antigen-Challenged Allergic Mice

• Published in: Clinical immunology and immunopathology 1995-04, Vol.75 (1), p.75-83
• Main Authors: Garlisi, Charles G., Falcone, Angela, Kung, Ted T., Stelts, Dawn, Pennline, Kenneth J., Beavis, Andrew J., Smith, Sidney R., Egan, Robert W., Umland, Shelby P.
• Format: Article
• Language: English
• ISSN: 0090-1229; 1090-2341
• DOI: 10.1006/clin.1995.1055

In a murine model of pulmonary inflammation, aerosolized antigen challenge of sensitized B6D2F1 mice leads to eosinophil accumulation within the lungs. Little is known of the role of T cells and their cytokine products in these allergic animals. In this study, we show that T cells migrate into the lungs in response to antigen challenge and are necessary for local production of cytokines (IL-4 and IL-5) important in B and T cell development as well as eosinophil activation and differentiation. Flow cytometry revealed an increase in the percentage of Thy1 + T cells but not in B220 + B cells in bronchoalveolar lavage fluid after challenge when compared to unchallenged mice. Although there was an increase in both T cell subsets, there were twice as many CD4 + cells as CD8 + cells at 24 hr and after 48 hr the CD4 + subset predominated. The CD4 + T lymphocytes were CD44 + CD45RB lo indicating an activated/memory phenotype and tracheobroncheal lymph node cells obtained from challenged mice proliferated in a dose-dependent manner in response to antigen stimulation in vitro. Reverse transcriptase-polymerase chain reaction analysis of lung tissue-derived RNA indicated an increase in Th 2-like cytokines. IL-4 and IL-5 steady-state mRNAs were at peak levels 6 hr after challenge, while no consistent increase was found for IFN-γ/mRNA levels. Treatment with the glucocorticoid betamethasone just prior to challenge reduced the levels of cytokine mRNA as well as the eosinophil influx. In vivo depletion of T cells from sensitized mice reduced pulmonary eosinophilia as well as the expression of IL-4, IL-5, and IFN-γ, steady-state mRNAs in the lungs of sensitized and challenged mice. These results indicate that T cells migrating into the lungs of mice after antigen challenge play an important role in the production of Th 2-like cytokines and the accumulation of eosinophils in bronchial fluids.