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Published in: Critical Care 1/2010

Open Access 01-02-2010 | Research

The relationship between CD4+CD25+CD127- regulatory T cells and inflammatory response and outcome during shock states

Authors: François Hein, Frédéric Massin, Aurélie Cravoisy-Popovic, Damien Barraud, Bruno Levy, Pierre-Edouard Bollaert, Sébastien Gibot

Published in: Critical Care | Issue 1/2010

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Abstract

Introduction

Although regulatory T lymphocytes (Tregs) have a pivotal role in preventing autoimmune diseases and limiting chronic inflammatory conditions, they may also block beneficial immune responses by preventing sterilizing immunity to certain pathogens.

Methods

To determine whether naturally occurring Treg cells have a role in inflammatory response and outcome during shock state we conducted an observational study in two adult ICUs from a university hospital. Within 12 hours of admission, peripheral whole blood was collected for the measurement of cytokines and determination of lymphocyte count. Sampling was repeated at day three, five and seven. Furthermore, an experimental septic shock was induced in adult Balb/c mice through caecal ligation and puncture.

Results

Forty-three patients suffering from shock (26 septic, 17 non septic), and 7 healthy volunteers were included. The percentage of Tregs increased as early as 3 days after the onset of shock, while their absolute number remained lower than in healthy volunteers. A similar pattern of Tregs kinetics was found in infected and non infected patients. Though there was an inverse correlation between severity scores and Tregs percentage, the time course of Tregs was similar between survivors and non survivors. No relation between Tregs and cytokine concentration was found. In septic mice, although there was a rapid increase in Treg cells subset among splenocytes, antibody-induced depletion of Tregs before the onset of sepsis did not alter survival.

Conclusions

These data argue against a determinant role of Tregs in inflammatory response and outcome during shock states.
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Literature
1.
go back to reference Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States; analysis of incidence, outcome and associated costs of care. Crit Care Med 2001, 29: 1303-1310. 10.1097/00003246-200107000-00002CrossRefPubMed Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States; analysis of incidence, outcome and associated costs of care. Crit Care Med 2001, 29: 1303-1310. 10.1097/00003246-200107000-00002CrossRefPubMed
2.
go back to reference Brun-Buisson C, Meshaka P, Pinton P, Vallet B, EPISEPSIS Study Group: EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med 2004, 30: 580-588. 10.1007/s00134-003-2121-4CrossRefPubMed Brun-Buisson C, Meshaka P, Pinton P, Vallet B, EPISEPSIS Study Group: EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med 2004, 30: 580-588. 10.1007/s00134-003-2121-4CrossRefPubMed
3.
go back to reference Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med 2003, 348: 138-150. 10.1056/NEJMra021333CrossRefPubMed Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med 2003, 348: 138-150. 10.1056/NEJMra021333CrossRefPubMed
4.
go back to reference Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE: Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med 1997, 25: 1298-1307. 10.1097/00003246-199708000-00015CrossRefPubMed Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE: Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med 1997, 25: 1298-1307. 10.1097/00003246-199708000-00015CrossRefPubMed
5.
go back to reference Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T: Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 2006, 212: 8-27. 10.1111/j.0105-2896.2006.00427.xCrossRefPubMed Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T: Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 2006, 212: 8-27. 10.1111/j.0105-2896.2006.00427.xCrossRefPubMed
7.
go back to reference Shevach EM: Regulatory T cells in autoimmmunity. Annu Rev Immunol 2000, 18: 423-449. 10.1146/annurev.immunol.18.1.423CrossRefPubMed Shevach EM: Regulatory T cells in autoimmmunity. Annu Rev Immunol 2000, 18: 423-449. 10.1146/annurev.immunol.18.1.423CrossRefPubMed
9.
go back to reference Monneret G, Venet F, Pachot A, Lepape A: Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med 2008, 14: 64-78. 10.2119/2007-00102.MonneretPubMedCentralCrossRefPubMed Monneret G, Venet F, Pachot A, Lepape A: Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med 2008, 14: 64-78. 10.2119/2007-00102.MonneretPubMedCentralCrossRefPubMed
10.
go back to reference Venet F, Pachot A, Debard AL, Bohé J, Bienvenu J, Lepape A, Monneret G: Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes. Crit Care Med 2004, 32: 2329-2331.PubMed Venet F, Pachot A, Debard AL, Bohé J, Bienvenu J, Lepape A, Monneret G: Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes. Crit Care Med 2004, 32: 2329-2331.PubMed
11.
go back to reference Heuer JG, Zhang T, Zhao J, Ding C, Cramer M, Justen KL, Vonderfecht SL, Na S: Adoptive transfer of in vitro-stimulated CD4+CD25+ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis. J Immunol 2005, 174: 7141-7146.CrossRefPubMed Heuer JG, Zhang T, Zhao J, Ding C, Cramer M, Justen KL, Vonderfecht SL, Na S: Adoptive transfer of in vitro-stimulated CD4+CD25+ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis. J Immunol 2005, 174: 7141-7146.CrossRefPubMed
12.
go back to reference Scumpia PO, Delano MJ, Kelly KM, O'Malley KA, Efron PA, McAuliffe PF, Brusko T, Ungaro R, Barker T, Wynn JL, Atkinson MA, Reeves WH, Salzler MJ, Moldawer LL: Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis. J Immunol 2006, 177: 7943-7949.CrossRefPubMed Scumpia PO, Delano MJ, Kelly KM, O'Malley KA, Efron PA, McAuliffe PF, Brusko T, Ungaro R, Barker T, Wynn JL, Atkinson MA, Reeves WH, Salzler MJ, Moldawer LL: Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis. J Immunol 2006, 177: 7943-7949.CrossRefPubMed
13.
go back to reference Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohé J, Lepape A, Ayala A, Monneret G: Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med 2009, 35: 678-686. 10.1007/s00134-008-1337-8PubMedCentralCrossRefPubMed Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohé J, Lepape A, Ayala A, Monneret G: Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med 2009, 35: 678-686. 10.1007/s00134-008-1337-8PubMedCentralCrossRefPubMed
14.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101: 1644-1655. 10.1378/chest.101.6.1644CrossRefPubMed Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101: 1644-1655. 10.1378/chest.101.6.1644CrossRefPubMed
15.
go back to reference Antonelli M, Levy M, Andrews PJD, Chastre J, Hudson LD, Manthous C, Meduri GU, Moreno RP, Putensen C, Stewart T, Torres A: Hemodynamic monitoring in shock and implications for management. International consensus conference, Paris, France, 27-28 April 2006. Intensive Care Med 2007, 33: 575-590. 10.1007/s00134-007-0531-4CrossRefPubMed Antonelli M, Levy M, Andrews PJD, Chastre J, Hudson LD, Manthous C, Meduri GU, Moreno RP, Putensen C, Stewart T, Torres A: Hemodynamic monitoring in shock and implications for management. International consensus conference, Paris, France, 27-28 April 2006. Intensive Care Med 2007, 33: 575-590. 10.1007/s00134-007-0531-4CrossRefPubMed
16.
go back to reference McCabe WR, Jackson GG: Gram negative bacteremia: I. Etiology and ecology. Arch Intern Med 1962, 110: 845-847. McCabe WR, Jackson GG: Gram negative bacteremia: I. Etiology and ecology. Arch Intern Med 1962, 110: 845-847.
17.
go back to reference Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 271: 2957-2963. 10.1001/jama.270.24.2957CrossRef Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 271: 2957-2963. 10.1001/jama.270.24.2957CrossRef
18.
go back to reference Vincent JL, de Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med 1998, 26: 1793-1800.CrossRefPubMed Vincent JL, de Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med 1998, 26: 1793-1800.CrossRefPubMed
19.
go back to reference Monneret G, Debard AL, Venet F, Bohe J, Hequet O, Bienvenu J, Lepape A: Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis. Crit Care Med 2003, 31: 2068-2071. 10.1097/01.CCM.0000069345.78884.0FCrossRefPubMed Monneret G, Debard AL, Venet F, Bohe J, Hequet O, Bienvenu J, Lepape A: Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis. Crit Care Med 2003, 31: 2068-2071. 10.1097/01.CCM.0000069345.78884.0FCrossRefPubMed
20.
go back to reference Oberholzer A, Oberholzer C, Moldawer LL: Sepsis syndromes: understanding the role of innate and acquired immunity. Shock 2001, 16: 83-96. 10.1097/00024382-200116020-00001CrossRefPubMed Oberholzer A, Oberholzer C, Moldawer LL: Sepsis syndromes: understanding the role of innate and acquired immunity. Shock 2001, 16: 83-96. 10.1097/00024382-200116020-00001CrossRefPubMed
21.
go back to reference Giamarellos-Bourboulis EJ, Tsaganos T, Spyridaki E, Mouktaroudi M, Plachouras D, Vaki I, Karagianni V, Antonopoulou A, Veloni V, Giamarellou H: Early changes of CD4-positive lymphocytes and NK cells in patients with severe Gram-negative sepsis. Crit Care 2006, 10: R166. 10.1186/cc5111PubMedCentralCrossRefPubMed Giamarellos-Bourboulis EJ, Tsaganos T, Spyridaki E, Mouktaroudi M, Plachouras D, Vaki I, Karagianni V, Antonopoulou A, Veloni V, Giamarellou H: Early changes of CD4-positive lymphocytes and NK cells in patients with severe Gram-negative sepsis. Crit Care 2006, 10: R166. 10.1186/cc5111PubMedCentralCrossRefPubMed
Metadata
Title
The relationship between CD4+CD25+CD127- regulatory T cells and inflammatory response and outcome during shock states
Authors
François Hein
Frédéric Massin
Aurélie Cravoisy-Popovic
Damien Barraud
Bruno Levy
Pierre-Edouard Bollaert
Sébastien Gibot
Publication date
01-02-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc8876

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