title: T cells are necessary for Th2 cytokine production and eosinophil accumulation in airways of antigen-challenged allergic mice.
abstract: 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+ CD45RBlo 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 Th2-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-gamma 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-gamma 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 Th2-like cytokines and the accumulation of eosinophils in bronchial fluids.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
authors.forename: C G
authors.initials: CG
authors.lastname: Garlisi
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: T T
authors.initials: TT
authors.lastname: Kung
authors.forename: D
authors.initials: D
authors.lastname: Stelts
authors.forename: K J
authors.initials: KJ
authors.lastname: Pennline
authors.forename: A J
authors.initials: AJ
authors.lastname: Beavis
authors.forename: S R
authors.initials: SR
authors.lastname: Smith
authors.forename: R W
authors.initials: RW
authors.lastname: Egan
authors.forename: S P
authors.initials: SP
authors.lastname: Umland
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology*; D018960:Hyaluronan Receptors; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007518:Isoantibodies / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D011014:Pneumonia / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D002352:Carrier Proteins; D016207:Cytokines; D018960:Hyaluronan Receptors; D015848:Interleukin-5; D007518:Isoantibodies; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; C035678:anti-Thy antibody; D015847:Interleukin-4