Circulating Treg cells expressing TNF receptor type 2 contributes to sepsis-induced immunosuppression in patients during sepsis shock.

Background Septic shock remains a major cause of death that can be complicated by a long-term impairment in immune function defining immunosuppression induced by sepsis (IS). Among Treg cells, the tumor necrosis factor receptor 2 positive (TNFR2 pos) Treg cell subset endorses significant immunosuppressive functions in human tumors and in a sepsis mouse model but have not been investigated during septic shock in humans. Methods We prospectively enrolled patients with septic shock hospitalized in Intensive Care Unit (ICU). We performed immunophenotyping and functional tests of CD4+T cells, Treg cells and TNFR2 posTregcells, on blood samples collected at 1, 4 and 7 days after admission in ICU. Results We investigated 10 patients with septic shock and compared to 10 healthy controls. Although the proportions of circulating Tregcells and TNFR2 posTregcells subsets were not increased, their CTLA-4 expression and suppressive functions in vitro were increased at 4 days of septic shock. Also, PBMC from healthy donors cultured with serum from septic shock patients had increased CTLA4 expression in TNFR2 pos Treg cells compared to TNFR2 neg Treg cells. Conclusion In patients with septic shock, CTLA-4 expression and suppressive function were increased in circulating TNFR2 posTreg cells. We identify TNFR2 posTreg cells as a potential attractive target for therapeutic intervention.