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Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis
Guillaume Monneret1, Anne-Lise Debard, Fabienne Venet
1Lyon-Sud University Hospital, France. guillaume.monneret@chu-lyon.fr
Objective:
Immunoparalysis has recently emerged as a possible cause explaining the failure of clinical trials in septic shock. Because human peripheral blood CD4+CD25+ T cells have been characterized as suppressor T cells, we hypothesized they might be increased in sepsis-induced immunoparalysis.
Design:
Prospective, observational, clinical study.
Setting:
Adult intensive care units in a university hospital.
Subjects:
Patients with septic shock (n = 16) and healthy individuals (n = 36).
Interventions:
None.
Measurements And Main Results:
In patients with septic shock (mortality rate at 28 days, 56%; mean admission Simplified Acute Physiology Score II, 47), we first illustrated immunoparalysis by showing a severe diminished monocytic human leukocyte antigen (HLA)-DR expression. Afterward, compared with control values, we found in these patients a marked elevation of circulating CD4+CD25+ T cells that were also CD45RO+ and CD69- and overexpressed CTLA-4. Importantly, nonsurvivors (n = 9) presented prolonged lower monocytic HLA-DR expression and higher percentage of CD4+CD25+ T-suppressor T cells.
Conclusions:
These data support the concept that the persistence of a pronounced immunoparalysis after septic shock is associated with a poor outcome. Whether CD4+CD25+ T cells directly participate in sepsis-induced immunoparalysis remains to be investigated.