CD28 costimulation is critical for experimental allergic asthma in HLA-DQ8 transgenic mice

Svetlana P. Chapoval, Chella S. David

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The objective of this study was to investigate the contribution of the CD28 costimulatory molecules to allergen-induced primary and chronic inflammatory responses. To this end, we have developed and characterized a short ragweed allergen-induced asthma model involving sensitization of HLA-DQ transgenic mice followed by intranasal challenge with allergen. Forty-eight hours after primary challenge, sensitized DQ8 mice developed pulmonary eosinophilic inflammation, airway hyperreactivity, Th2 cytokines, and IgE/IgG1 Ab. This allergic inflammatory response was absent in H-2Aβ0 and DQ8/CD280 mice. Secondary rechallenge with allergen 4 weeks later induced even greater inflammatory changes in the airways of DQ8 mice with eosinophils being the predominant inflammatory cells while only pulmonary lymphocytosis was observed in DQ8/CD280 mice. No inflammation was detected in H-2Aβ0 mice. Proliferation and cytokine profile studies demonstrated that CD28 regulates T-cell activation and effector function. Therefore, CD28 is essential for the extrinsic asthma and can be a target for immunotherapy.

Original languageEnglish (US)
Pages (from-to)83-94
Number of pages12
JournalClinical Immunology
Volume106
Issue number2
DOIs
StatePublished - Feb 1 2003

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Keywords

  • Allergy
  • Co-stimulation
  • HLA
  • Inflammation
  • MHC
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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