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

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

doi:10.3390/biomedicines9060616

Abstract

Conversion of CD4+CD25+FOXP3+ T regulatory cells (Tregs) from the immature (CD45RA+) to mature (CD45RO+) phenotype has been shown during development and allergic reactions. The relative frequencies of these Treg phenotypes and their responses to oxidative stress during development and allergic inflammation were analysed in samples from paediatric and adult subjects. The FOXP3lowCD45RA+ population was dominant in early childhood, while the percentage of FOXP3highCD45RO+ 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+CD25high 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 Tregs from adults with asthma. Finally, CD4+CD25high cells from paediatric subjects were more sensitive to oxidative stress than those from adults in vitro. The differential Treg sensitivity to oxidative stress observed in children and adults was likely dependent on phenotypic CD45 isoform switching. Increased sensitivity of Treg 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.

Highlights

As shown in representative cases, the percentage of CD4+ CD25+ FOXP3+ T cells that were CD45RO+ was lower in the 1-year-old control and the 1-year-old allergic subject no. 2 that had both food allergy and atopic dermatitis than that in the allergic subject no. 3, an 9.7-year-old child with paediatric allergic asthma (Figure 1b)
In agreement with previous studies, FOXP3 expression was much higher in the CD45RO+ population than in the CD45RA+ population (Figure 1c) [11]
Developmental T regulatory cells (Tregs) phenotypic switching occurs in early childhood, which may be a consequence of exposure to extrinsic antigens such as bacteria and viruses

Summary

Introduction

The relative frequencies of these Treg phenotypes and their responses to oxidative stress during development and allergic inflammation were analysed in samples from paediatric and adult subjects. The FOXP3low CD45RA+ population was dominant in early childhood, while the percentage of FOXP3high CD45RO+ cells began increasing in the first year of life. These phenotypic changes were observed in subjects with and without asthma. CD4+ CD25high cells from paediatric subjects were more sensitive to oxidative stress than those from adults in vitro. Increased sensitivity of Treg cells from adults with asthma to H2 O2 resulted from a reduction of peroxiredoxin-2, -3, -4 and increased pERK1/2 via impaired Ca2+ response in these cells.

Methods

Results

Conclusion