Interleukin-12 induces interferon-γ expression and natural killer cytotoxicity in cord blood mononuclear cells

Abstract

Severe viral infection in newborns has been attributed to immaturity of the immune system including a defect in natural killer cytotoxicity (NKC) and decreased production of cytokines that are important for natural killer (NK) function. We investigated the induction of interferon (IFN)-γ and activation of NK activity in adult and cord blood mononuclear cells (BMC) after IL-12 treatment. The levels of mRNA in these BMC were measured by Northern blot and reverse transcription polymerase chain reactions using primers specific for IFN-γ. The levels of IFN-γ protein were measured by ELISA. In the absence of IL-12, only adult BMC spontaneously produced low levels of IFN-γ. After IL-12 treatment, induction of IFN-γ expression was detected as early as 4 h in both cord and adult BMC. Both cord and adult cells showed similar levels of IFN-γ mRNA and protein expression in response to IL-12 at a concentration as low as 10 U/mL. In contrast, upon phorbol ester and ionomycin treatment, adult BMC produced more IFN-γ mRNA than cord BMC. In a 51Cr release assay with human immunodeficiency-infected H9 cells as indicators, both cord and adult cells responded to IL-12 induction of NKC. Our findings demonstrate that cord BMC are capable of responding to IL-12 stimulation, competent in synthesizing IFN-γ, and able to mount NKC. Thus, it appears that the deficiency in IFN-γ production or NKC in cord cells is not due to an inherent defect in IL-12 response of the cord cells.