Asthma is induced by intranasal coadministration of allergen and natural killer T-cell ligand in a mouse model.
BACKGROUND
Allergic asthma is an inflammatory lung disease caused by a T(H)2-driven immune response. However, intranasal exposures to soluble antigen lead to mucosal tolerance, and the mechanism involved in generation of T(H)2 responses to inert inhaled allergens is unknown.


OBJECTIVE
The aim of this study was to investigate whether CD1d-restricted natural killer T (NKT) cells can contribute to the induction of T(H)2-dependent allergic asthma in a mouse model.


METHODS
To investigate the effect of NKT cells on the development of asthma, NKT cell ligand, alpha-galactosylceramide (alphaGC), was used with antigens. We intranasally sensitized Balb/c mice with various combinations of antigen and alphaGC 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 alphaGC together, and ovalbumin inhalation.


RESULTS
Only when immunized with ovalbumin plus alphaGC, airway hyperreactivity, airway eosinophils, elevated IgE level, and T(H)2-cytokine production were observed in Balb/c mice. Ovalbumin alone, alphaGC alone, or BSA plus alphaGC-immunized mice did not induce asthma. Studies in NKT cell-deficient, or CD4(+) T-cell-deficient mice intranasally exposed to ovalbumin plus alphaGC did not show the development of asthma. An increase of NKT cells in bronchoalveolar lavage was observed in the pathologic states.


CONCLUSIONS
These data demonstrate that NKT cells can play crucial roles in allergen sensitization and pathologic states in asthma. Furthermore, our new asthma model using alphaGC will be very useful to induce asthma and to dissect the role of NKT cells and other cells in asthma.
Kim
Jae-Ouk
JO
Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Kim
Dong-Hyeon
DH
Chang
Woo-Sung
WS
Hong
Changwan
C
Park
Se-Ho
SH
Kim
Sanghee
S
Kang
Chang-Yuil
CY
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology*; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D001249:Asthma / Q000209:etiology*; D016535:Bronchial Hyperreactivity / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin