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 prevalenc e of allergic respiratory diseases, particularly amongst children. This stu dy 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 t o specific allergens and tetanus toroid in blood samples from atopic and no n-atopic infants every 6 months from birth to 2 years of age. Cytokine anal yses of responses to housedust-mite allergen used ELISA and reverse-transcr iptase PCR. We also measured responses to Fel dl(cat allergen) and tetanus toroid. Findings Samples from 18 atopic and 13 non-atopic infants showed low-level Th2-skewed allergen-specific responses at birth, with little accompanying s pecific interferon-gamma production. Neonatal Th2 responses were lower in t he atopic group than in the non-atopic group; the differences were signific ant for interleukin-4 (mRNA: beta-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 respo nses during the first year of life in non-atopic children, but there was co nsolidation of responses in atopic children, associated with defective neon atal interferon-gamma production. Interpretation The continuation of fetal allergen-specific Th2 responses du ring infancy is a defining feature of the inductive phase of atopic disease , and is associated with decreased capacity for production of the Th1 cytok ine interferon gamma by atopic neonates. These findings provide a plausible mechanism for persistence of the fetal Th2 responses during early childhoo d in atopic individuals and subsequent expression of disease.