Staphylococcus aureus convert neonatal conventional CD 4 + T cells into FOXP 3 + CD 25 + CD 127 low T cells via the PD ‐1/ PD ‐ L 1 axis

Summary The gut microbiota provides an important stimulus for the induction of regulatory T ( T reg) cells in mice, whether this applies to newborn children is unknown. In S wedish children, S taphylococcus aureus has become a common early colonizer of the gut. Here, we sought to study the effects of bacterial stimulation on neonatal CD 4 + T cells for the induction of CD 25 +   CD 127 low T reg cells in vitro . The proportion of circulating CD 25 +   CD 127 low Treg cells and their expression of FOXP 3, H elios and CTLA ‐4 was examined in newborns and adults. To evaluate if commensal gut bacteria could induce T reg cells, C ell T race violet‐stained non‐ T reg cells from cord or peripheral blood from adults were co‐cultured with autologous CD 25 +   CD 127 low Treg cells and remaining mononuclear cells and stimulated with S . aureus . Newborns had a significantly lower proportion of CD 25 +   CD 127 low Treg cells than adults, but these cells were H elios + and CTLA ‐4 + to a higher extent than in adults. FOXP 3 +   CD 25 +   CD 127 low T cells were induced mainly in neonatal C ell T race‐stained non‐ T reg cells after stimulation with S . aureus . In cell cultures from adults, S . aureus induced CD 25 +   CD 127 low T cells only if sorted naive CD 45 RA + non‐ T reg cells were used, but these cells expressed less FOXP 3 than those induced from newborns. Sorted neonatal CD 25 +   CD 127 low T cells from S . aureus ‐stimulated cultures were still suppressive. Finally, blocking PD ‐ L 1 during stimulation reduced the induction of FOXP 3 +   CD 25 +   CD 127 low T cells. These results suggest that newborns have a higher proportion of circulating thymically derived H elios + T reg cells than adults and that S . aureus possess an ability to convert neonatal conventional CD 4 + T cells into FOXP 3 +   CD 25 + CD 127 low T reg cells via the PD ‐1/ PD ‐ L 1 axis.