Postnatal development of respiratory mucosal immune function in the rat: regulation of IgE responses to inhaled allergen

Abstract

Repeated exposure of immunocompetent adult rats to aerosolised allergen stimulates persistent IgG responses to the allergen, the magnitude of which varies as a function of genetic background. In contrast, exposed adult animals develop immunological tolerance in the IgE isotype, and are unable to produce allergen‐specific IgE antibody in response to subsequent parenteral immunization. Infant rats appear anergic to challenge with inhaled allergen either in relation to IgG synthesis or expression of tolerance in the IgE antibody class, and both these functions were subsequently acquired during the first week after weaning. Systemic immune responses were essentially normal in the infant animals, suggesting that the failure to ‘recognise’ inhaled antigen in the early postnatal period was due to a selective maturational defect in local respiratory mucosal immune function.

Development of the airway intraepithelial dendritic cell network in the rat from class II major histocompatibility (Ia)-negative precursors: differential regulation of Ia expression at different levels of the respiratory tract.

“…For example, local antigenic challenge of the gastrointestinal mucosa in newborn experimental animals effectively "primes" the T cell system for subsequent hypersensitivity responses (5,6), whereas comparable challenge of the respiratory mucosa in infant animals fails to elicit a T cell response (7). Similarly, the capacity to develop protective oral tolerance to dietary antigens appears within a few days of birth (5), whereas the parallel process in the respiratory tract does not operate effectively until after weaning (7,8), despite the attainment of adult-equivalent levels of systemic T cell competence well before this time. These latter findings suggest that site-specific developmental factors can play an important role in the induction and expression of T cell immunity within individual tissue microenvironments, during early postnatal life.…”

Is Allergy a Preventable Disease?

“…Animal studies suggest that the neonatal mucosal tolerance induction mechanisms are malfunctional 5 Moreover, cross-sectional [6][7] and prospective 8 studies strongly indicate that exposure to allergens early in life may have an impact on the incidence of allergy many years later. Thus, an understanding of the development of immune responses to allergens is a prerequisite for the understanding of why the prevalence of allergy is increasing in developed countries and for the implementation of primary prevention.…”