Surface Phenotype Changes and Increased Response to Oxidative Stress in CD4+CD25high T Cells

Yoshiki Yamamoto; Takaharu Negoro; Rui Tada; Michiaki Narushima; Akane Hoshi; Yoichi Negishi; Yasuko Nakano

doi:10.3390/biomedicines9060616

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

Biomedicines. 2021 May 29;9(6):616. doi: 10.3390/biomedicines9060616.

Authors

Yoshiki Yamamoto¹, Takaharu Negoro², Rui Tada³, Michiaki Narushima⁴, Akane Hoshi², Yoichi Negishi³, Yasuko Nakano²

Affiliations

¹ Department of Paediatrics, Tokyo Metropolitan Ebara Hospital, Tokyo 145-0065, Japan.
² Department of Pharmacogenomics, School of Pharmacy, Showa University, Tokyo 142-8555, Japan.
³ Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
⁴ Department of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa 224-8503, Japan.

Abstract

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.

Keywords: CD45 isoform; allergy; extracellular signal-regulated kinases 1/2; oxidative stress; regulatory T cell.

Abstract

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