Circulating Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Contribute to Sepsis-Induced Immunosuppression in Patients During Septic Shock. (21st May 2021)

• Record Type: Journal Article
• Authors: Gaborit, Benjamin Jean; Chaumette, Tanguy; Chauveau, Marie; Asquier-Khati, Antoine; Roquilly, Antoine; Boutoille, David; Josien, Régis; Salomon, Benoit L; Asehnoune, Karim
• Is Part Of: Journal of infectious diseases. Volume 224:Number 12(2021)
• Page Start: 2160
• Page End: 2169
• Publication Date: 2021-05-21
• Subjects: circulating Treg cells -- septic shock -- TNFR2 -- immunosuppression; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab276
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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 pos Treg cells. We identify TNFR2 pos Treg cells as a potential attractive target for therapeutic intervention. Abstract : In patients with septic shock, Treg and TNFR2 pos Treg cells acquire early an activated phenotype and a suppressive activity. Blocking TNFR2 on Treg cells is thus an attractive therapeutic target to overcome sepsis-induced immunosuppression.