T cells are necessary for Th2 cytokine production and eosinophil accumulation in airways of antigen-challenged allergic mice

Clin Immunol Immunopathol. 1995 Apr;75(1):75-83. doi: 10.1006/clin.1995.1055.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens / administration & dosage
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Carrier Proteins / genetics
  • Cytokines / metabolism*
  • Eosinophils / cytology*
  • Hyaluronan Receptors
  • Immunologic Memory
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Isoantibodies / pharmacology
  • Lung / immunology
  • Lung / pathology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred Strains
  • Phenotype
  • Pneumonia / immunology
  • Receptors, Cell Surface / genetics
  • Receptors, Lymphocyte Homing / genetics
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Th2 Cells / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Carrier Proteins
  • Cytokines
  • Hyaluronan Receptors
  • Interleukin-5
  • Isoantibodies
  • Receptors, Cell Surface
  • Receptors, Lymphocyte Homing
  • anti-Thy antibody
  • Interleukin-4