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

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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+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.

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Acknowledgments

Aspects of the work presented here were supported by funds from the Hospices Civils de Lyon (to G.M.) and a grant from the NIH R01 GM46354 (to A.A.). The study was conducted thanks to the logistic support of Centre d’Investigation Clinique (CIC 201) of INSERM and Hospices Civils de Lyon. None of the authors has any potential financial conflict of interest related to this manuscript.

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Authors and Affiliations

  1. Division of Surgical Research, Rhode Island Hospital, Brown University, Providence, RI, USA

    Fabienne Venet, Chun-Shiang Chung & Alfred Ayala

  2. Flow Cytometry Unit, Immunology Laboratory, Hôpital E. Herriot, Hospices Civils de Lyon, 5, Place d’Arsonval, 69437, Lyon Cedex 03, France

    Hakim Kherouf, Anne Geeraert, Chistophe Malcus, Françoise Poitevin & Guillaume Monneret

  3. Intensive Care Units, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France

    Julien Bohé & Alain Lepape

Authors
  1. Fabienne Venet
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  2. Chun-Shiang Chung
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  3. Hakim Kherouf
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  4. Anne Geeraert
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  5. Chistophe Malcus
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  6. Françoise Poitevin
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  7. Julien Bohé
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  8. Alain Lepape
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  9. Alfred Ayala
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  10. Guillaume Monneret
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Correspondence to Guillaume Monneret.

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Venet, F., Chung, CS., Kherouf, H. et al. Increased circulating regulatory T cells (CD4+CD25+CD127−) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med 35, 678–686 (2009). https://doi.org/10.1007/s00134-008-1337-8

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  • DOI: https://doi.org/10.1007/s00134-008-1337-8

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