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(low)CD45RA(+) population was dominant in early childhood, while the percentage of FOXP3(high)CD45RO(+) 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(2)O(2))-treated CD4(+)CD25(high) cells in adults with asthma compared with those without asthma. Increased pERK1/2 levels corresponded with increased Ca(2+) 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 H(2)O(2) resulted from a reduction of peroxiredoxin-2, -3, -4 and increased pERK1/2 via impaired Ca(2+) response in these cells.