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 (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.