Original

Intensive Care Medicine

, Volume 35, Issue 4, pp 678-686

Increased circulating regulatory T cells (CD4+CD25+CD127) contribute to lymphocyte anergy in septic shock patients

  • Fabienne VenetAffiliated withDivision of Surgical Research, Rhode Island Hospital, Brown University
  • , Chun-Shiang ChungAffiliated withDivision of Surgical Research, Rhode Island Hospital, Brown University
  • , Hakim KheroufAffiliated withFlow Cytometry Unit, Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon
  • , Anne GeeraertAffiliated withFlow Cytometry Unit, Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon
  • , Chistophe MalcusAffiliated withFlow Cytometry Unit, Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon
  • , Françoise PoitevinAffiliated withFlow Cytometry Unit, Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon
  • , Julien BohéAffiliated withIntensive Care Units, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon
  • , Alain LepapeAffiliated withIntensive Care Units, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon
  • , Alfred AyalaAffiliated withDivision of Surgical Research, Rhode Island Hospital, Brown University
    • , Guillaume MonneretAffiliated withFlow Cytometry Unit, Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon Email author 

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Abstract

Purpose

Sepsis syndrome represents the leading cause of death in intensive care unit. Patients present features consistent with a decline in immune responsiveness potentially contributing to mortality. We investigated whether CD4+CD25+ regulatory T cells (Treg) participate in the induction of lymphocyte anergy after sepsis.

Method

Observational study in septic shock patients and experimental study in mice.

Results

We took advantage of the recently described flow cytometric gating strategy using the measurement of CD25 and CD127 expressions for monitoring Treg (CD4+CD25+CD127Foxp3+). In patients the increased circulating Treg percentage significantly correlated with a decreased lympho-proliferative response. In a murine model of sepsis mimicking these observations, the ex vivo downregulation of Foxp3 expression using siRNA was associated with a restoration of this response.

Conclusion

The relative increase in circulating Treg might play a role in lymphocyte anergy described after septic shock and represent a standardizable surrogate marker of declining proliferative capacity after sepsis.

Keywords

Septic shock Anergy CD4+CD25+ CD127 Regulatory T cells Foxp3