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Staphylococcus aureus convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) T cells via the PD-1/PD-L1 axis

Artikel i vetenskaplig tidskrift
Författare Hardis Rabe
Inger Nordström
Kerstin Andersson
Anna-Carin Lundell
Anna Rudin
Publicerad i Immunology
Volym 141
Nummer/häfte 3
Sidor 467-481
ISSN 0019-2805
Publiceringsår 2014
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Sidor 467-481
Språk en
Länkar dx.doi.org/10.1111/imm.12209
Ämnesord cord blood, FOXP3(+) regulatory T cells, Helios, programmed cell death 1, Staphylococcus aureus, TRANSCRIPTION FACTOR FOXP3, REGULATORY CELLS, INTESTINAL COLONIZATION, DENDRITIC CELLS, CORD BLOOD, IN-VIVO, INDUCTION, TOLERANCE, RESPONSES, ANTIGEN
Ämneskategorier Klinisk medicin

Sammanfattning

The gut microbiota provides an important stimulus for the induction of regulatory T (Treg) cells in mice, whether this applies to newborn children is unknown. In Swedish children, Staphylococcus aureus has become a common early colonizer of the gut. Here, we sought to study the effects of bacterial stimulation on neonatal CD4(+) T cells for the induction of CD25(+)CD127(low) Treg cells in vitro. The proportion of circulating CD25(+)CD127(low) Treg cells and their expression of FOXP3, Helios and CTLA-4 was examined in newborns and adults. To evaluate if commensal gut bacteria could induce Treg cells, CellTrace violet-stained non-Treg cells from cord or peripheral blood from adults were co-cultured with autologous CD25(+)CD127(low) Treg cells and remaining mononuclear cells and stimulated with S.aureus. Newborns had a significantly lower proportion of CD25(+)CD127(low) Treg cells than adults, but these cells were Helios(+) and CTLA-4(+) to a higher extent than in adults. FOXP3(+)CD25(+)CD127(low) T cells were induced mainly in neonatal CellTrace-stained non-Treg cells after stimulation with S.aureus. In cell cultures from adults, S.aureus induced CD25(+)CD127(low) T cells only if sorted naive CD45RA(+) non-Treg cells were used, but these cells expressed less FOXP3 than those induced from newborns. Sorted neonatal CD25(+)CD127(low) T cells from S.aureus-stimulated cultures were still suppressive. Finally, blocking PD-L1 during stimulation reduced the induction of FOXP3(+)CD25(+)CD127(low) T cells. These results suggest that newborns have a higher proportion of circulating thymically derived Helios(+) Treg cells than adults and that S.aureus possess an ability to convert neonatal conventional CD4(+) T cells into FOXP3(+)CD25(+) CD127(low) Treg cells via the PD-1/PD-L1 axis.

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