Neonates at risk of atopy show impaired production of interferon-gamma after stimulation with bacterial products (LPS and SEE)
Recent studies demonstrate reduced interferon-gamma (IFN-gamma) secretion in neonates who became atopic later in life. The underlying pathomechanism is still unknown. We therefore examined the effects of bacterial products on neonatal IFN-gamma production acting through different T-cell- or antigen-presenting-cell (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a combination of both and restimulated with PMA and ionomycin. LPS and SEE as single stimuli induced IFN-gamma production to the same extent in CBMC of neonates with high and low risk of atopy. In contrast, a combination of LPS and SEE had a multiplying effect on IFN-gamma secretion only in CBMC of neonates with low risk of atopy. Phenotype analysis revealed that only memory T cells showed impaired IFN-gamma synthesis (median 3.6% IFN-gamma-producing cells vs 14.2% in controls: P < 0.01), whereas IFN-gamma production by naive T cells did not differ in either group. Taken together, these results point to the existence of a disturbed function of costimulatory mechanisms in neonates at high risk of atopy, provoking reduced memory T-cell IFN-gamma production.
Pohl
D
D
Klinik für Kinder- und Jugendmedizin der Ruhr-Universität im St. Josef Hospital, Bochum, Germany.
Bockelmann
C
C
Förster
K
K
Rieger
C H
CH
Schauer
U
U
D017951:Antigen Presentation; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism*; D007156:Immunologic Memory; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015759:Ionomycin / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology
D004768:Enterotoxins; D008070:Lipopolysaccharides; C049463:enterotoxin E, Staphylococcal; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate