Surface Phenotype Changes and Increased Response to Oxidative Stress in CD4⁺CD25^high T Cells

Conversion of CD4⁺CD25⁺FOXP3⁺ T regulatory cells (T_regs) from the immature (CD45RA⁺) to mature (CD45RO⁺) phenotype has been shown during development and allergic reactions. The relative frequencies of these T_reg phenotypes and their responses to oxidative stress during development and allergic inflammation were analysed in samples from paediatric and adult subjects. The FOXP3^lowCD45RA⁺ population was dominant in early childhood, while the percentage of FOXP3^highCD45RO⁺ 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 (H₂O₂)-treated CD4⁺CD25^high cells in adults with asthma compared with those without asthma. Increased pERK1/2 levels corresponded with increased Ca²⁺ response to T cell receptor stimulation. mRNA expression of peroxiredoxins declined in T_regs from adults with asthma. Finally, CD4⁺CD25^high cells from paediatric subjects were more sensitive to oxidative stress than those from adults in vitro. The differential T_reg sensitivity to oxidative stress observed in children and adults was likely dependent on phenotypic CD45 isoform switching. Increased sensitivity of T_reg cells from adults with asthma to H₂O₂ resulted from a reduction of peroxiredoxin-2, -3, -4 and increased pERK1/2 via impaired Ca²⁺ response in these cells.