The role of CD28-B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma

J. L. Lordan, D. E. Davies, S. J. Wilson, G. Dent, A. Corkhill, Z. Jaffar, K. Roberts, R. Djukanović, S. T. Holgate

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: T cells play an important role in airway inflammation in asthma through the release of TH2 cytokines. Optimal T-cell activation by antigen-presenting cells requires costimulatory signaling, such as the interaction of CD80, CD86, or both with CD28. In patients with mild allergic asthma, the fusion protein cytotoxic T-lymphocyte antigen 4Ig (CTLA-4Ig), which inhibits CD28-mediated signaling, blocks the release of IL-5 and IL-13 from bronchial explant cultures exposed to the allergen Dermatophagoides pteronyssinus. Objectives: To assess costimulation in more severe forms of atopic asthma, we have compared the ability of CTLA-4Ig to block allergen-induced cytokine responses of bronchial explants and PBMCs from patients with moderately severe asthma. Methods: Bronchial explants and PBMCs were cultured in vitro, and cytokine expression was measured by means of quantitative RT-PCR and ELISA. Results: Constitutive mRNA transcripts for IL-5, IL-13, and GM-CSF were detected in the tissue explants, but only IL-5 mRNA increased significantly with allergen stimulation. Consistent with increased transcription, allergen-stimulated IL-5 protein release into explant supernatants, but this was not blocked by CTLA-4Ig. Allergen did not induce GM-CSF release, and IL-13 protein could not be detected in the explant supernatants under any condition. In contrast, allergen enhanced production of IL-5 and IL-13 by PBMC cultures from the same subjects, and this was inhibited effectively by CTLA-4Ig. Conclusions: These data suggest that IL-5 production in the airways of subjects with moderately severe asthma is largely independent of CD28-mediated costimulation. The different requirements for CD28-mediated costimulation in PBMC cultures and bronchial tissue cultures emphasizes the importance of the tissue microenvironment in pulmonary inflammatory responses in severe asthma.

Original languageEnglish
Pages (from-to)976-981
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume108
Issue number6
DOIs
StatePublished - 2001

Keywords

  • Allergen
  • Asthma
  • CD28
  • CTLA-4
  • Costimulation
  • Explant
  • IL
  • Inflammation
  • T cell

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