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Defective IL2 gene expression in newborn is accompanied with impaired tyrosine-phosphorylation in T cells
H Ansart-Pirenne1, N Soulimani, E Tartour
1Laboratoire d'Immunologie, Hôpital Robert Debré, Paris, France.
Insights
Newborn T cells show defective interleukin-2 (IL2) mRNA expression due to impaired tyrosine phosphorylation signaling after CD3 stimulation. This suggests a molecular basis for reduced immune responses in neonates.
Area of Science:
- Immunology
- Molecular Biology
- Neonatal Research
Background:
- Interleukin-2 (IL2) mRNA expression is crucial for T cell function.
- CD3 stimulation initiates T cell signaling pathways, including protein-tyrosine phosphorylation.
- Neonatal T cells exhibit impaired IL2 production, but the underlying molecular mechanisms are not fully understood.
Purpose of the Study:
- To investigate whether defective IL2 response to CD3 stimulation in newborns is associated with altered tyrosine phosphorylation.
- To compare CD3-induced tyrosine phosphorylation in newborn (cord) and adult T cells.
Main Methods:
- Comparative analysis of CD3-induced tyrosine phosphorylation in peripheral lymphocytes and CD4 T cells from cord blood and adults.
- Immunoblotting using an antiphosphotyrosine antibody.
- Assessment of tyrosine phosphorylation intensity using pervanadate (phosphatase inhibitor) during CD3 stimulation.
Main Results:
- CD3 stimulation induced tyrosine phosphorylation in both newborn and adult T cells.
- Tyrosine phosphorylation was detectable within minutes of CD3 ligation.
- A significant decrease in the intensity of CD3-induced tyrosine phosphorylation was observed in cord blood T cells compared to adult cells.
Conclusions:
- Suboptimal tyrosine phosphorylation signaling in neonatal T cells may contribute to defective IL2 production.
- Impaired protein-tyrosine phosphorylation is a potential mechanism underlying the reduced immune responsiveness of newborn T cells.
Abstract:
Here we confirmed that IL2 mRNA expression in CD3-stimulated T cells is defective at birth. Because protein-tyrosine phosphorylation is an important part of signaling through CD3 and plays a key role in IL2 transcription, we further investigated whether impaired IL2 response to CD3 in newborns would be accompanied with an alteration of tyrosine phosphorylation. In this purpose, CD3-induced tyrosine phosphorylation was evaluated comparatively in newborn and adult cells by immunoblotting of total cellular extract with an antiphosphotyrosine antibody. Results show that, in both peripheral lymphocytes or purified CD4 T cells from both cord and adult, CD3 stimulation could induce small even significant tyrosine-phosphorylation. Tyrosine phosphorylation occurs as soon as 2' following CD3 ligation and was still evident up to 15-20'. Yet, by using a highly sensitive method to analyze CD3-induced accumulation of phosphorylated substrates, which consisted in adding pervanadate, an inhibitor of phosphatases, during the last 2 min of CD3 stimulation, we showed that the intensity of tyrosine phosphorylation was clearly decreased in cord cells. From these results, it is tempting to speculate that suboptimal capacities of cord T cells to up-regulate tyrosine phosphorylation might contribute to defective IL2 production in neonates.