Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants

By adulthood there is almost universal immunological memory to aeroallergen s, and the presence of allergic disease appears to be related to the nature of the underlying T-helper (Th) cell cytokine responses. The hypothesis of this study is that adult patterns of allergen specific Th-cell memory (Th- 2 polarized in atopics vs. Th1 in non-atopics) can be determined in early i nfancy. Mononuclear cell cytokine responses to house-dust mite were measured at 6-m onthly intervals from birth to 2 years of age, using ELISA (IL-10, IL-13, I FN-gamma) and sqRT/PCR (IL-4, IL-5, IL-9, IFN-gamma) in normal infants (n = 14) with no family history or allergic symptoms, and infants with a family history and definite atopy by 2 years (n = 16). Both normals and atopics showed low-level Th2 skewed allergen-specific resp onses at birth with little accompanying IFN-gamma. The Th2 responses to hou se-dust mite were higher in normal newborns, who then show a rapid downregu lation of these responses in the first year of life. Atopic infants instead show a consolidation of their neonatal patterns of Th2 polarized allergen specific immunity. Earlier studies indicate that neonates at high risk of atopy display dimini shed capacity for production of the Th1 cytokine IFN-gamma. The present stu dy suggests for the first time that neonates who subsequently develop atopy also initially have reduced capacity to mount Th2 responses. However, in c ontrast to non-atopics who selectively downregulate their fetal Th2 polariz ed allergen-specific responses, atopic children display age-associated upre gulation of Th2 immunity.