| Summary: | Conversion of CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> T regulatory cells (T<sub>regs</sub>) from the immature (CD45RA<sup>+</sup>) to mature (CD45RO<sup>+</sup>) phenotype has been shown during development and allergic reactions. The relative frequencies of these T<sub>reg</sub> phenotypes and their responses to oxidative stress during development and allergic inflammation were analysed in samples from paediatric and adult subjects. The FOXP3<sup>low</sup>CD45RA<sup>+</sup> population was dominant in early childhood, while the percentage of FOXP3<sup>high</sup>CD45RO<sup>+</sup> cells began increasing in the first year of life. These phenotypic changes were observed in subjects with and without asthma. Further, there was a significant increase in phosphorylated ERK1/2 (pERK1/2) protein in hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-treated CD4<sup>+</sup>CD25<sup>high</sup> cells in adults with asthma compared with those without asthma. Increased pERK1/2 levels corresponded with increased Ca<sup>2+</sup> response to T cell receptor stimulation. mRNA expression of peroxiredoxins declined in T<sub>regs</sub> from adults with asthma. Finally, CD4<sup>+</sup>CD25<sup>high</sup> cells from paediatric subjects were more sensitive to oxidative stress than those from adults in vitro. The differential T<sub>reg</sub> sensitivity to oxidative stress observed in children and adults was likely dependent on phenotypic CD45 isoform switching. Increased sensitivity of T<sub>reg</sub> cells from adults with asthma to H<sub>2</sub>O<sub>2</sub> resulted from a reduction of peroxiredoxin-2, -3, -4 and increased pERK1/2 via impaired Ca<sup>2+</sup> response in these cells.
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