Circulating Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Contribute to Sepsis-Induced Immunosuppression in Patients During Septic Shock

Background. Septic shock remains a major cause of death that can be complicated by long-term impairment in immune function. Among regulatory T (Treg) cells, the tumor necrosis factor receptor 2 positive (TNFR2(pos)) Treg-cell subset endorses significant immunosuppressive functions in human tumors and a sepsis mouse model but has not been investigated during septic shock in humans. Methods. We prospectively enrolled patients with septic shock hospitalized in intensive care units (ICU). We performed immunophenotyping and functional tests of CD4(+) T cells, Treg cells, and TNFR2(pos) Treg cells on blood samples collected 1,4, and 7 days after admission to ICU. Results. We investigated 10 patients with septic shock compared to 10 healthy controls. Although the proportions of circulating Treg cells and TNFR2(pos) Treg-cell subsets were not increased, their CTLA4 expression and suppressive functions in vitro were increased at 4 days of septic shock. Peripheral blood mononuclear cells 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. Conclusions. In patients with septic shock, CTLA4 expression and suppressive function were increased in circulating TNFR2(po)(s) Treg cells. We identify TNFR2(po)(s) Treg cells as a potential attractive target for therapeutic intervention.

Automated summary

The study found that CTLA4 expression and suppressive function were increased in circulating TNFR2(pos) Treg cells in patients with septic shock, suggesting the potential of TNFR2(pos) Treg cells as a target for therapeutic intervention.