Genetic 'risk' for atopy is associated with delayed postnatal maturation of T-cell competence.
Recent in vitro studies suggest that IgE production in adults is co-ordinately regulated by negative signals from gamma IFN-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 gamma IFN 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.
Holt
P G
PG
Western Australian Research Institute for Child Health, Subiaco.
Clough
J B
JB
Holt
B J
BJ
Baron-Hay
M J
MJ
Rose
A H
AH
Robinson
B W
BW
Thomas
W R
WR
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D002675:Child, Preschool; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007121:Immunocompetence; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D012307:Risk Factors; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma