Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis

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 11, 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 CD45R0+ 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.