Defective IFN-gamma production in the human neonate. I. Dysregulation rather than intrinsic abnormality.

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Abstract
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.