Interleukin-4 is required for the induction of lung Th2 mucosal immunity

• Published in: American journal of respiratory cell and molecular biology Vol. 13; no. 1; pp. 54 - 59
• Main Authors: Coyle, AJ, Le Gros, G, Bertrand, C, Tsuyuki, S, Heusser, CH, Kopf, M, Anderson, GP
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.07.1995; American Thoracic Society
• Subjects: AIDS/HIV; Animals; Cell Separation; Eosinophils - immunology; Flow Cytometry; Gene Deletion; Immunity, Cellular - immunology; Inflammation - etiology; Inflammation - immunology; Interleukin-4 - genetics; Interleukin-4 - immunology; Interleukin-4 - metabolism; Lung - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Mucous Membrane - immunology; Ovalbumin - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - cytology; Th2 Cells - immunology
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/ajrcmb.13.1.7598937

Aerosol antigen challenge of ovalbumin-sensitized mice induced an eosinophilic airway inflammation that was dependent on interleukin (IL)-5 and CD4+, but not CD8+, T lymphocytes. The involvement of the Th2 phenotype of CD4+ T cells was supported by demonstrating that FACS-sorted purified lung T cells from sensitized, but not control, mice produced IL-4, IL-5, and IL-10 after activation of the CD3/TCR complex. To determine the role of IL-4 in this process, we used mice in which the gene for IL-4 was deleted by homologous recombination. Antigen challenge of IL-4 gene-targeted mice resulted in a marked attenuation of eosinophilic inflammation and IL-5 secretion. To more fully understand the time when IL-4 was involved, we administered a neutralizing anti-IL-4 antibody (11B11) either immediately before antigen challenge or during immunization. Inhibition of IL-4 before antigen challenge had little effect on antigen-induced eosinophil infiltration. However, when 11B11 was administered during immunization, there was a marked reduction in eosinophil infiltration. Cross-linking of the CD3/TCR complex of FACS-sorted lung T cells revealed that only when anti-IL-4 was administered during immunization was there an inhibition of T cell-derived IL-5 and IgE production. These results suggest that IL-4 is central both to the induction of a local Th2 response and to the development of eosinophilic inflammation of the lung. Moreover, we suggest a sequential involvement of IL-4 and IL-5, with IL-4 committing naive T cells to a Th2 phenotype which upon activation by aerosol provocation secrete IL-5, resulting in eosinophil accumulation.