Db. Corry et al., REQUIREMENTS FOR ALLERGEN-INDUCED AIRWAY HYPERREACTIVITY IN T-CELL-DEFICIENT AND B-CELL-DEFICIENT MICE, Molecular medicine, 4(5), 1998, pp. 344-355
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Cell Biology
Background: The pathogenesis of asthma is believed to reflect antigen-
induced airway inflammation leading to the recruitment of eosinophils
and activation of mast cells through cell-associated IgE. Controversie
s persist however, regarding the relative importance of different path
ogenic cells and effector molecules. Materials and Methods: A variety
of gene-targeted mice were examined for the induction of cholinergic a
irway hyperresponsiveness (AH), allergic airway inflammation, mucus pr
oduction, and serum IgE reactivity following intratracheal challenge w
ith a potent allergen. AH was determined using whole-body plethysmogra
phy following acetylcholine challenge. Where possible, results were co
nfirmed using neutralizing antibodies and cell-specific reconstitution
of immune deficient mice. Results: T and B cell-deficient, recombinas
e-activating-gene-deficient mice (RAG -/-) failed to develop significa
nt allergic inflammation and AH following allergen challenge. Reconsti
tution of RAG -/- mice with CD4(+) T cells alone was sufficient to res
tore allergen-induced AH, allergic inflammation and goblet cell hyperp
lasia, but not IgE reactivity. Sensitized B cell-deficient mice also d
eveloped airway hyperreactivity and lung inflammation comparable to th
at of wild-type animals, confirming that antibodies were dispensable.
Treatment with neutralizing anti-IL-4 antibody or sensitization of IL-
4-deficient mice resulted in loss of airway hyperreactivity, whereas t
reatment with anti-IL-5 antibody or sensitization of IL-5-deficient mi
ce had no effect. Conclusions: In mice, CD4(+) T cells are alone suffi
cient to mediate many of the pathognomonic changes that occur in human
asthma by a mechanism dependent upon IL-4, but independent of IL-5, I
gE, or both. Clarification of the role played by CD4(+) T cells is lik
ely to stimulate important therapeutic advances in treatment of asthma
.