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

Lancet. 1999 Jan 16;353(9148):196-200. doi: 10.1016/S0140-6736(98)05104-6.


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 d1 (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-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 y 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Follow-Up Studies
  • Humans
  • Hypersensitivity, Immediate / genetics
  • Hypersensitivity, Immediate / immunology*
  • Immunologic Memory*
  • Infant
  • Infant, Newborn
  • Interferon-gamma / biosynthesis
  • Interleukins / biosynthesis
  • Lymphocyte Activation
  • Mites / immunology
  • Ovalbumin / immunology
  • Prospective Studies
  • Th2 Cells / immunology*


  • Allergens
  • Interleukins
  • Interferon-gamma
  • Ovalbumin