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Deficient interferon-alpha response of newborns in comparison to adults
1Institute of Immunology and Transfusion Medicine, University of Lübeck Medical School, FRG.
Abstract:
Human peripheral blood mononuclear cells (PBMC) respond efficiently to viral infections with interferon (IFN)-alpha production. Using Newcastle disease virus (NDV) and Sendai virus as inducers, our experiments with purified mononuclear cell populations of healthy adult volunteers showed that monocytes were the main IFN-alpha producers in these systems. Using an ELISA, which specifically recognized IFN-alpha 2, and a bioassay, in which all subtypes were detected, IFN-alpha 2 was a major subtype expressed. Furthermore, IFN-alpha release was higher after induction with NDV than after stimulation with Sendai virus. To compare the IFN-alpha response of adult PBMC to human cord blood mononuclear cells the cells were stimulated with NDV or Sendai virus. The IFN-alpha response of cord blood mononuclear cells to Sendai virus was slightly reduced compared to that of adult cells. However, IFN-alpha 2 was a major subtype produced. In contrast, when cord blood mononuclear cells were stimulated with NDV the IFN-alpha release was strongly diminished. Furthermore, IFN-alpha 2 was not the major subtype expressed. By in situ hybridization the number of IFN-alpha-producing cells was quantified. We found that 1% of adult PBMC and newborn leukocytes showed detectable IFN-alpha mRNA after stimulation with either Sendai virus or NDV. In conclusion, these data suggest that the ability of cord blood mononuclear cells to produce IFN-alpha is diminished compared to adult PBMC. This impaired IFN-alpha response is not based on a reduced number of IFN-alpha-producing cells, but rather due to underlying control mechanisms of the newborns that are different from the regulation of adult PBMC.
Insights
Human peripheral blood mononuclear cells (PBMC) produce interferon-alpha (IFN-alpha) in response to viral infections. Cord blood mononuclear cells show a diminished IFN-alpha response compared to adult PBMC, suggesting different regulatory mechanisms in newborns.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human peripheral blood mononuclear cells (PBMC) are crucial for antiviral defense through interferon-alpha (IFN-alpha) production.
- Monocytes are identified as the primary IFN-alpha producers in response to viral inducers like Newcastle disease virus (NDV) and Sendai virus.
- IFN-alpha 2 is a significant subtype produced, with varying levels depending on the inducer.
Purpose of the Study:
- To compare the IFN-alpha production capacity of adult PBMC with that of human cord blood mononuclear cells.
- To investigate the specific IFN-alpha subtypes produced by adult and cord blood cells.
- To determine the number of IFN-alpha-producing cells in both adult and newborn populations.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) for IFN-alpha 2 detection.
- Bioassay for detecting all IFN-alpha subtypes.
- In situ hybridization to quantify IFN-alpha mRNA-expressing cells.
Main Results:
- Adult PBMC showed robust IFN-alpha production upon stimulation with NDV and Sendai virus, with IFN-alpha 2 being a major subtype.
- Cord blood mononuclear cells exhibited a reduced IFN-alpha response to NDV, and IFN-alpha 2 was not the predominant subtype.
- The percentage of cells expressing IFN-alpha mRNA was similar (1%) in both adult and newborn leukocytes, irrespective of the viral inducer.
Conclusions:
- Cord blood mononuclear cells have a diminished capacity for IFN-alpha production compared to adult PBMC.
- The impaired IFN-alpha response in newborns is not due to a lower number of IFN-alpha-producing cells.
- Underlying regulatory mechanisms in newborns differ from those in adult PBMC, influencing IFN-alpha production.