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

The prevalence and severity of allergic diseases, in particular those affecting the respiratory system, are increasing 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) subjects stem from aberrant T cell responses to a range of airborne environmental antigens that seemingly are ignored by non-atopic individuals. At the T cell level, allergic reactivity manifests as production of a Th-2-1ike cytokine profile at each challenge (1, 2), and mounting evidence (reviewed 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 neonatal 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 underlying antigen-specific T cell cytokine responses during the induction and subsequent expression of classical neonatal tolerance. They demonstrate that neonatal antigen exposure triggers an initially heterogeneous T cell response containing 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 pattern 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.