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.


METHODS
Prospective, observational, clinical study.


METHODS
Adult intensive care units in a university hospital.


METHODS
Patients with septic shock (n = 16) and healthy individuals (n = 36).


METHODS
None.


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.
Monneret
Guillaume
G
Lyon-Sud University Hospital, France. guillaume.monneret@chu-lyon.fr
Debard
Anne-Lise
AL
Venet
Fabienne
F
Bohe
Julien
J
Hequet
Olivier
O
Bienvenu
Jacques
J
Lepape
Alain
A
D000069594:Abatacept; D015703:Antigens, CD / Q000097:blood; D000943:Antigens, Differentiation / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D015704:CD4 Antigens / Q000097:blood*; D060908:CTLA-4 Antigen; D003422:Critical Care; D016207:Cytokines / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood; D017052:Hospital Mortality; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D018796:Immunoconjugates; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000099192:CD69 Antigens
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; D016207:Cytokines; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C556706:CTLA4 protein, human