Genetic 'risk' for atopy is associated with delayed postnatal maturation of T-cell competence

P.G. Holt, J.B. Clough, B.J. Holt, M.J. Baron-Hay, Alison Rose, Bruce Robinson, W.R. Thomas

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235 Citations (Scopus)

Abstract

Recent in vitro studies suggest that IgE production in adults is co-ordinately regulated by negative signals from gammaIFN-producing CD4+ T-helper-1 (TH-1) and positive signals from IL-4 producing (TH-2) T-cells. Additionally, seroepidemiological evidence has pinpointed infancy as the period of maximum lifetime risk for T-cell sensitization to ubiquitous environmental antigens. The present study sought to elucidate the relationship between these observations, by examination of CD4+ T-cell function in normal children and those genetically at 'high risk' for atopy, spanning the age range (up to 4 years) in which IgE responses to environmental allergens is typically manifest. Immunocompetent T-cell precursor frequencies (determined by cloning at limiting dilution) were markedly reduced in 'high risk' children relative to normals (0.53 +/- 0.29 vs 0.26 +/- 0.19; P = 0.0025). Consistent with reports from other laboratories employing bulk T-cell culture techniques, the gammaIFN producing capacity of CD4+ T-cell clones from both groups of children were markedly reduced relative to adults, and was lowest in the high risk group (P <0.02). IL-4 production by CD4+ T-cell clones from the normal children was within the adult range, but again was significantly lower in the high risk group (P <0.00005). This indicates that initial immune responses to environmental allergens in early childhood occur against a background of maturational 'deficiency' in CD4+ T-cell function, and suggests the possibility that variations in the rate of postnatal maturation of T-cell competence may be a contributing factor in the development of differing patterns of immunological responsiveness to environmental allergens.
Original languageEnglish
Pages (from-to)1093-1099
JournalClinical and Experimental Allergy
Volume22
DOIs
Publication statusPublished - 1992

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