T-CELLS ARE NECESSARY FOR TH-2 CYTOKINE PRODUCTION AND EOSINOPHIL ACCUMULATION IN AIRWAYS OF ANTIGEN-CHALLENGED ALLERGIC MICE

In a murine model of pulmonary inflammation, aerosolized antigen chall enge 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 cell s migrate into the lungs in response to antigen challenge and are nece ssary for local production of cytokines (IL-4 and IL-5) important in B and T cell development as well as eosinophil activation and different iation. 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(+) c ells as CD8(+) cells at 24 hr and after 48 hr the CD4(+) subset predom inated. The CD4(+) T lymphocytes were CD44(+) CD45RB(lo) indicating an activated/memory phenotype and tracheobroncheal lymph node cells obta ined from challenged mice proliferated in a dose-dependent manner in r esponse to antigen stimulation in vitro. Reverse transcriptase-polymer ase chain reaction analysis of lung tissue-derived RNA indicated an in crease in Th-2-like cytokines. IL-4 and IL-5 steady-state mRNAs were a t peak levels 6 hr after challenge, while no consistent increase was f ound for IFN-gamma mRNA levels. Treatment with the glucocorticoid beta methasone just prior to challenge reduced the levels of cytokine mRNA as well as the eosinophil influx. In vivo depletion of T cells from se nsitized mice reduced pulmonary eosinophilia as well as the expression of IL-4, IL-5, and IFN-gamma steady-state mRNAs in the lungs of sensi tized and challenged mice. These results indicate that T cells migrati ng into the lungs of mice after antigen challenge play an important ro le in the production of Th-2-like cytokines and the accumulation of eo sinophils in bronchial fluids. (C) 1995 Academic Press, Inc.