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

Susan Prescott, C. Macaubas, T. Smallacombe, B.J. Holt, Peter Sly, P.G. Holt

Research output: Contribution to journalArticlepeer-review

809 Citations (Scopus)

Abstract

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 toroid 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 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 specific interferon-gamma production. Neonatal Th2 responses were lower in the atopic group than in the non-atopic group; the differences were significant 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 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-gamma 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 gamma 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.
Original languageEnglish
Pages (from-to)196-200
JournalLancet
Volume353
DOIs
Publication statusPublished - 1999

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