Development of allergen-specific T-cell memory in atopic and normal children

Background In the past 20–30 years, there has been an increase in prevalence of allergic respiratory diseases, particularly amongst children. This study is a prospective analysis of the postnatal maturation of T-helper cell (Th) responses to aeroallergens in atopic and non-atopic infants. Methods We measured mononuclear-cell proliferative and cytokine responses to specific allergens and tetanus toxoid in blood samples from atopic and non-atopic infants every 6 months from birth to 2 years of age. Cytokine analyses of responses to housedust-mite allergen used ELISA and reverse-transcriptase PCR. We also measured responses to Fel d 1 (cat allergen) and tetanus toxoid. Findings Samples from 18 atopic and 13 non-atopic infants showed low-level Th2-skewed allergen-specific responses at birth, with little accompanying specific interferon-γ production. Neonatal Th2 responses were lower in the atopic group than in the non-atopic group; the differences were significant for interleukin-4 (mRNA: β-actin ratio 0·48 [SE 0·15] vs 0·15 [0·06], p=0·049), interleukin-6 (4750 [48] vs 1352 [51] pg/mL culture fluid, p=0·003), interleukin-10 (1162 [228] vs 485 [89], p=0·015), and interleukin-13 (7·1 [0·9] vs 0·9 [0·3], p=0·008). There was rapid suppression of Th2 responses during the first year of life in non-atopic children, but there was consolidation of responses in atopic children, associated with defective neonatal interferon-γ production. Interpretation The continuation of fetal allergen-specific Th2 responses during infancy is a defining feature of the inductive phase of atopic disease, and is associated with decreased capacity for production of the Th1 cytokine interferon γ by atopic neonates. These findings provide a plausible mechanism for persistence of the fetal Th2 responses during early childhood in atopic individuals and subsequent expression of disease.