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

Crit Care Med. 2003 Jul;31(7):2068-71. doi: 10.1097/01.CCM.0000069345.78884.0F.


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.

MeSH terms

  • Abatacept
  • Antigens, CD / blood
  • Antigens, Differentiation / blood
  • Antigens, Differentiation, T-Lymphocyte / blood
  • CD4 Antigens / blood*
  • CTLA-4 Antigen
  • Critical Care*
  • Cytokines / blood*
  • Female
  • Flow Cytometry
  • HLA-DR Antigens / blood
  • Hospital Mortality
  • Humans
  • Immune Tolerance / immunology*
  • Immunoconjugates*
  • Lectins, C-Type
  • Leukocyte Common Antigens / blood
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Prognosis
  • Receptors, Interleukin-2 / blood*
  • Shock, Septic / immunology*
  • Shock, Septic / mortality
  • Survival Rate
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD69 antigen
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • HLA-DR Antigens
  • Immunoconjugates
  • Lectins, C-Type
  • Receptors, Interleukin-2
  • Abatacept
  • Leukocyte Common Antigens