Genetic ‘risk’ for atopy is associated with delayed postnatal maturation of T‐cell competence

Abstract

Recent in vitro studies suggest that IgE production in adults is co‐ordinately regulated by negative signals from γIFN‐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 γIFN 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+ T‐cell clones from the normal children was within the adult range, but again was significantly lower in the high risk group (P+ 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.