| First Author | Coyle AJ | Year | 1995 |
| Journal | Am J Respir Cell Mol Biol | Volume | 13 |
| Issue | 1 | Pages | 54-9 |
| PubMed ID | 7598937 | Mgi Jnum | J:113065 |
| Mgi Id | MGI:3664398 | Doi | 10.1165/ajrcmb.13.1.7598937 |
| Citation | Coyle AJ, et al. (1995) Interleukin-4 is required for the induction of lung Th2 mucosal immunity. Am J Respir Cell Mol Biol 13(1):54-9 |
| abstractText | 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. |
