• Damien Guinault, Marie-Laure Nicolau-Travers, Stein Silva, Olivier Cointault, Barnabé Daniau, Arnaud Del Bello, Michael Peres, David Rousset, Julie Rieunier, Laurence Lavayssiere, Marie-Béatrice Nogier, Edith Hourcastagnou, Arnaud Mari, Nassim Kamar, François Vergez, and Stanislas Faguer.
• Département de Néphrologie et Transplantation d'organes-Unité de Réanimation, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
• Crit. Care Med. 2021 Sep 1; 49 (9): 1513-1523.

RationaleThere is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis.DesignObservational prospective study.SettingTwo ICUs in a teaching hospital (France).PatientsEighty patients with sepsis admitted to the ICU.InterventionsQuantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ).Measurements And Main ResultsUsing unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes.ConclusionsEasy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

26 keywords...

hide…