Defective IFN-gamma production in the human neonate. I. Dysregulation rather than intrinsic abnormality.
Cord blood leukocytes (CBL) stimulated with PHA, Con A, or with the monoclonal antibody OKT3 proliferate normally but produce very low titers of IFN-gamma. This defect was not observed with maternal leukocytes collected at the time of delivery, indicating that the defective production of IFN-gamma in CBL is not a mere consequence of a hormonal change associated with labor. CBL produced large amounts of IFN-gamma (comparable to those observed in adult control and in mothers) after stimulation with staphylococcal enterotoxin A (SEA). Furthermore, gamma-irradiation with as little as 500 or 1000 rad, or incubation at 37 degrees C for 24 hr, reversed the defect in PHA-induced IFN-gamma secretion. This finding indicates that the defective secretion of IFN-gamma of CBL is not intrinsic, but rather is the consequence of a subtle dysregulation. We could not find evidence for a defective accessory function with cord blood monocytes, because the addition of adherent cells from adult donors did not reverse the defect. In co-cultures of adult leukocytes and CBL, PHA-induced IFN-gamma secretion was comparable to that of adult cultures tested alone. Nonirradiated CBL were not able to suppress IFN-gamma secretion by irradiated autologous leukocytes. Together, our results suggest that the defective PHA-induced IFN-gamma secretion of CBL is the result of an original type of dysregulation and is associated with an excessive sensitivity to suppressive signals rather than excessive suppressor function.
D000328:Adult; D000367:Age Factors; D000911:Antibodies, Monoclonal; D003208:Concanavalin A; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis*; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D011247:Pregnancy; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003208:Concanavalin A; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate