Primary allergic sensitization to environmental antigens: perinatal T cell priming as a determinant of responder phenotype in adulthood.

Open Access
Publisher Website
Google Scholar
Abstract
T he prevalence and severity of allergic diseases, in par- ticular those affecting the respiratory system, are in- creasing at an alarming rate in the developed countries, and the international research effort into the etiology and pathogenesis of these syndromes is rapidly expanding to meet this challenge. The immunoinflammatory reactions that mediate airway tissue damage in allergic (atopic) sub- jects stem from aberrant T cell responses to a range of air- borne environmental antigens that seemingly are ignored by non-atopic individuals. At the T cell level, allergic reac- tivity manifests as production of a Th-2-1ike cytokine pro- file at each challenge (1, 2), and mounting evidence (re- viewed briefly below) suggests that the development of this pattern of T cell sensitization is frequently associated with exposure to high levels of the relevant antigens during early infancy. This finding contrasts with the traditional experimental literature, in which parenteral antigenic challenge of neo- natal animals leads preferentially to tolerance induction, a process most commonly ascribed to T cell anergy and/or deletion (3-5). However in this issue of the journal, Singh et al. (6) present the results of a comprehensive study from a murine model, which focuses on the pattern of underly- ing antigen-specific T cell cytokine responses during the induction and subsequent expression of classical neonatal tolerance. They demonstrate that neonatal antigen expo- sure triggers an initially heterogeneous T cell response con- taining both Th-1- and Th-2-like elements, which results not in eventual T cell deletion/anergy but instead in "priming" for subsequent immune deviation toward a pat- tern ofT cell immunity that is skewed toward Th-2. Their discussion of the relevance of this neonatal tolerance model is couched specifically in terms of autoimmune diseases. However, as argued below, the underlying T cell selection process is equally relevant to the etiology of human allergic diseases.