Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies

Abstract

Human neonatal lymphocytes produced little macrophage activation factor in response to mitogens. This correlated with decreased production of interferon-gamma (IFNγ): adult lymphokines contained 894.2 ± 177.1 U/ml, whereas neonatal cord and peripheral lymphokines contained 66.9 ± 17.0 and 116.7 ± 29.6 U/ml by bioassay. Results by radioimmunoassay (RIA) for IFNγ were similar. In contrast, the interleukin 2 content of cord lymphokines was greater (P < 0.01) and that of neonatal peripheral blood lymphokines similar to that of adults. Interleukin 1 production and interleukin 2 receptor expression and affinity were similar for adult and neonatal cells. Interleukins 1 and 2 in amounts comparable to those in adult lymphokines did not increase production of macrophage activation factor or IFNγ by neonatal cells. Neonatal cells did not contain intracellular IFN or degrade exogenous IFN. Excess suppressor activity was not found in neonatal cultures. Addition of IFNα, 10,000-50,000 Uml of interleukin 2 or phorbol myristate acetate (PMA) to cord mononuclear cells or of adult monocytes or PMA to cord T cells increased IFNγ production compared to cells stimulated with concanavalin A (ConA) alone. Nevertheless, under optimal conditions (T cells + PMA + Con A), adult cells produced much more IFNγ (1,360 ± 261 U/ml by RIA) than cord cells (122 ± 37 U/ml). Staphylococcal enterotoxin A (SEA) stimulated cord cell IFNγ production at low cell densities; nevertheless, adult cells produced more IFN in response to SEA (1,341 ± 350 U/ml) than cord cells (350 ± 33 U/ml). Decreased production of IFNγ by neonatal cells appears to be due both to differences in their intrinsic capacity to produce IFNγ and to differences in regulatory mechanisms.