High level interleukin-12 production, but diminished interferon-γ production, by cord blood mononuclear cells

Abstract

Cell-mediated immunity (CMI) in neonates is relatively deficient when compared with adults. Defects in cytokine production and/or regulation may contribute to heightened susceptibility to infection by intracellular pathogens. The heterodimeric cytokine IL-12 is a key regulator of CMI and inducer of interferon-γ (IFN-γ) production. We report here that umbilical cord blood-derived mononuclear cells (MNC) are capable of producing IL-12 (p40 subunit, measured by RIA, and IL-12 p70 heterodimer, by ELISA) at levels comparable to or greater than adult peripheral blood MNC, after stimulation with heat-killed Staphylococcus aureus in 18-h cultures. As in adult MNC, S. aureus induced IL-12 p40 mRNA accumulation in cord blood MNC. IFN-γ was also produced in the S. aureus-stimulated cultures, in an IL-12-dependent manner, but cord blood MNC produced 5-fold lower levels of IFN-γ compared with adult MNC (p < 0.05). Preincubation with IL-10 inhibited IL-12 p40 production by cord blood and adult peripheral blood MNC in a dose-dependent fashion, whereas neutralization of endogenous IL-10 enhanced IL-12 and IFN-γ levels. The results demonstrate that the relative CMI deficiency in neonates is not due to an intrinsic defect in the capacity of neonatal MNC to produce IL-12. The underlying factors responsible for diminished IFN-γ production are not known, but may lie in the balance of stimulatory and inhibitory signals delivered to the IFN-γ secreting cells along with IL-12, or may relate more to the absence of memory T cells among cord blood MNC.