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

Intensive Care Med. 2009 Apr;35(4):678-86. doi: 10.1007/s00134-008-1337-8. Epub 2008 Oct 23.


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(+)CD127(-)Foxp3(+)). 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Apoptosis / physiology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Energy Metabolism / physiology*
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Interleukin-7 Receptor alpha Subunit / immunology*
  • Male
  • Middle Aged
  • Shock, Septic / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Antigens, Differentiation, T-Lymphocyte
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit