Abstract
ABSTRACT: Newborns are more susceptible to fungal, viral, protozoan, and certain bacterial infections than adults. This susceptibility is due in part to a decreased interferon gamma (IFγ) production. The present investigation focuses on the role of the IL-2 receptor in the deficient IFγ production in neonatal T cells. IL-2-induced IFγ production in unstimulated neonatal cord blood and adult peripheral T cells was comparable, but the IFγ production in CD3-stimulated neonatal T cells was only 20% of the adult production. Neonatal and adult T cells showed no difference in the expression of the 55-kD α and 75-kD β chains of the IL-2 receptor. Blocking of the 55-kD α chain of the IL2 receptor with TAC MAb resulted in a marginal reduction in IFγ release from unstimulated or CD3-stimulated neonatal T cells cultured in the presence of IL-2. In contrast, blocking of the 55-kD α chain of the IL-2 receptor in adult T cells caused a 92% and 73% inhibition in IFγ production in unstimulated and stimulated T cells, respectively. Blocking of the 75-kD β chain of the IL-2 receptor with TU27 MAb had a marginal effect in both unstimulated and CD3-stimuIated neonatal and adult lymphocytes. Binding studies with unstimulated cord blood T cells using [125I]-IL-2 showed a binding affinity that corresponded with the intermediate affinity IL-2 receptor. In CD3-stimulated cord blood T cells, a high-affinity receptor was found. The addition of TAC MAb blocked binding to the high-affinity receptor and resulted in IL-2 binding with intermediate affinity. Northern analysis showed an IL-2-induced accumulation of IFγ mRNA in unstimulated and stimulated neonatal T cells. In contrast to adult T lymphocytes, TAC MAb did not cause a decrease in IL-2-induced IFγ mRNA expression in CD3-stimulated neonatal lymphocytes. These data suggest that cord blood T lymphocytes express normal IL-2 receptors and are able to form a functional intact high-affinity IL-2 receptor complex. However, neonatal T cells do not up-regulate IFγ production in response to IL-2.
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von Freeden, U., Zessack, N., van Valen, F. et al. Defective Interferon Gamma Production in Neonatal T Cells Is Independent of Interleukin-2 Receptor Binding. Pediatr Res 30, 270–275 (1991). https://doi.org/10.1203/00006450-199109000-00015
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DOI: https://doi.org/10.1203/00006450-199109000-00015