Mechanisms preventing allergen-induced airways hyperreactivity: Role of tolerance and immune deviation JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Tsitoura, D. C., Blumenthal, R. L., Berry, G., DeKruyff, R. H., Umetsu, D. T. 2000; 106 (2): 239-246


Aeroallergens continuously enter the respiratory tract of atopic individuals and provoke the development of asthma characterized by airway hyperreactivity (AHR) and inflammation. By contrast, nonatopic individuals are exposed to the same aeroallergens, but airway inflammation does not develop. However, the mechanisms that prevent allergen-induced respiratory diseases in nonatopic subjects are poorly characterized.In this study we compared the role of allergen-specific T-cell tolerance and immune deviation in conferring protection against the development of allergen-induced AHR.We exposed mice to intranasal ovalbumin (OVA) to induce T-cell tolerance and examined its effects on the subsequent development of AHR and inflammation.We demonstrated that exposure of mice to intranasal OVA resulted in peripheral CD4(+) T-cell unresponsiveness that very efficiently prevented not only the development of AHR but also greatly inhibited airway inflammation and OVA-specific IgE production. The induction of peripheral T-cell tolerance and protection against AHR were not dependent on the presence of IFN-gamma or IL-4. The development of AHR was also prevented by an OVA-specific T(H)1-biased immune response induced by inhalation of OVA in the presence of IL-12. However, the OVA-specific T(H)1 response was associated with a significant degree of pulmonary inflammation.These results indicate that both allergen-specific T-cell tolerance and T(H)1-biased immune deviation prevent the development of AHR, but T(H)1 responses are associated with significantly greater inflammation in the lung than is associated with T-cell unresponsiveness. Therefore CD4(+) T-cell unresponsiveness critically regulates immune responses to aeroallergens and protects against the development of allergic disease and asthma.

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