T-cell mediated late increase in bronchial tone after allergen provocation in a murine asthma model.
Allergen inhalation by sensitized asthmatics induces an IgE and mast cell dependent bronchoconstriction and a Th2-dependent inflammatory airway reaction, mucus hypersecretion and airway hyperreactivity. The link between T cells and bronchoconstriction remains controversial. Here we analyzed allergen-induced changes in airway tone in ovalbumin-sensitized mice with established allergic airway inflammation. Inhalation of nebulized ovalbumin elicited a dose-dependent and allergen-specific increase in airway resistance and bronchial tone with a concomitant increase of lymphocytes and eosinophils in bronchoalveolar lavage fluid. A Th2 pattern of cytokine expression and increased mRNA expression of MCP-1, RANTES and VCAM-1 were demonstrated. Anti-CD4 monoclonal antibody treatment prior to provocation decreased IL-13 and VCAM-1 mRNA expression and abolished the increase in bronchial tone and the inflammatory response. We conclude that allergen inhalation in sensitized mice induces airway narrowing similar to the late asthmatic reactions in humans and that this phenomenon is based on activation of CD4(+) T cells.
Meyts
Isabelle
I
Division of Clinical Immunology, Katholieke Universiteit Leuven, Belgium. Isabelle.Meyts@uz.kuleuven.be
Vanoirbeek
Jeroen A
JA
Hens
Greet
G
Vanaudenaerde
Bart M
BM
Verbinnen
Bert
B
Bullens
Dominique M A
DM
Overbergh
Lut
L
Mathieu
Chantal
C
Ceuppens
Jan L
JL
Hellings
Peter W
PW
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D000485:Allergens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016207:Cytokines; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D010047:Ovalbumin