An antigen-independent but not antigen-specific TH1 response provides protection in the murine airway inflammation model

Atopic disorders are associated with an imbalanced TH cell response biased toward a strong TH2 type, resulting in excessive production of IgE antibodies, eosinophil recruitment and activation, and mast cell degranulation. Restoring the TH1-TH2 balance by increasing the antigen-specific TH1 response...

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Veröffentlicht in:Journal of allergy and clinical immunology 2004-12, Vol.114 (6), p.1301-1308
Hauptverfasser: Burger, Melissa S., Zuleger, Cindy L., Chu, Qili, Gao, Xiaoyan, Payne, Lendon G., Chen, Dexiang
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Sprache:eng
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Zusammenfassung:Atopic disorders are associated with an imbalanced TH cell response biased toward a strong TH2 type, resulting in excessive production of IgE antibodies, eosinophil recruitment and activation, and mast cell degranulation. Restoring the TH1-TH2 balance by increasing the antigen-specific TH1 response has been pursued for specific allergy immunotherapy. Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG) are strong TH1 adjuvants and are being investigated for allergy immunotherapy. This study was designed to investigate the protective role of antigen-specific TH1 responses induced by epidermal powder immunization with ovalbumin (OVA) and CpG in a murine airway inflammation model. An allergy model was used in which BALB/c mice were sensitized and then challenged with OVA. Mice received prophylactic or therapeutic immunizations with OVA, CpG, or both. After challenge, pulmonary inflammation and cell infiltration were measured on the basis of BAL cell counts and lung histology. Immune response was determined by measuring the levels of lavage cytokines and serum antibodies. Coadministration of OVA and CpG by means of subcutaneous injection or epidermal powder immunization, although inducing a strong TH1 response, neither suppressed TH2 cytokines nor offered protection against pulmonary eosinophilia and histopathology in a mouse challenge model. However, when CpG was used as a stand-alone treatment of previously sensitized animals, protection against allergic airway inflammation was observed. After challenge with OVA, eosinophilia was suppressed in the lungs of the CpG-treated mice. This finding argues against the approach of boosting an allergen-dependent TH1 response and favors induction of an antigen-independent TH1 response for allergy immunotherapy.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2004.08.013