Asthma is induced by intranasal coadministration of allergen and natural killer T-cell ligand in a mouse model

Jae Ouk Kim, Dong Hyeon Kim, Woo Sung Chang, Changwan Hong, Se-Ho Park, Sanghee Kim, Chang Yuil Kang

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49 Citations (Scopus)

Abstract

Allergic asthma is an inflammatory lung disease caused by a T H2-driven immune response. However, intranasal exposures to soluble antigen lead to mucosal tolerance, and the mechanism involved in generation of T H2 responses to inert inhaled allergens is unknown. The aim of this study was to investigate whether CD1d-restricted natural killer T (NKT) cells can contribute to the induction of T H2-dependent allergic asthma in a mouse model. To investigate the effect of NKT cells on the development of asthma, NKT cell ligand, α-galactosylceramide (αGC), was used with antigens. We intranasally sensitized Balb/c mice with various combinations of antigen and αGC for 3 consecutive days and challenged them 2 weeks later with an aerosol of ovalbumin. NKT cell-deficient or T H cell-deficient mice were immunized by administering ovalbumin and αGC together, and ovalbumin inhalation. Only when immunized with ovalbumin plus αGC, airway hyperreactivity, airway eosinophils, elevated IgE level, and T H2-cytokine production were observed in Balb/c mice. Ovalbumin alone, αGC alone, or BSA plus αGC-immunized mice did not induce asthma. Studies in NKT cell-deficient, or CD4 + T-cell-deficient mice intranasally exposed to ovalbumin plus αGC did not show the development of asthma. An increase of NKT cells in bronchoalveolar lavage was observed in the pathologic states. These data demonstrate that NKT cells can play crucial roles in allergen sensitization and pathologic states in asthma. Furthermore, our new asthma model using αGC will be very useful to induce asthma and to dissect the role of NKT cells and other cells in asthma.

Original languageEnglish
Pages (from-to)1332-1338
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume114
Issue number6
DOIs
Publication statusPublished - 2004 Dec 1

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Keywords

  • α-galactosylceramide
  • asthma
  • Natural killer T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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