Skip to main content

Additional bad news from regulatory T cells in sepsis

We would like to revisit the commentary by Christaki and Patrozou [1] on regulatory T cells (Tregs) as significant modulators of various immune responses after severe injury. Indeed, we would like to add some very recent references that strongly reinforce their results.

Strong evidence indicates that, in septic conditions, increases in Tregs have deleterious consequences. In septic shock patients, augmented levels of Tregs significantly and inversely correlated with decreased lymphocyte proliferation [2]. This phenomenon, recapitulated after cecal ligation and puncture (CLP) in mice, was totally abrogated by using Foxp3 small interfering RNA (Foxp3 is a specific Treg transcription factor). In a similar model [3], after mild CLP, mice presented with immunosuppression that dampened defenses against secondary infectious challenge (Legionella pneumophilia inoculation 15 days after CLP). The restoration of efficient responses against infection was achieved thanks to anti-glucocorticoid-induced TNF receptor antibodies, known to abrogate Treg-mediated suppression. Lastly, a recent paper published in Blood [4] reported that sepsis-induced immunosuppression resulted in a reduced immune tolerance that facilitated the rapid growth of solid tumors. Foxp3+ Tregs were responsible for this effect. Although tumors were subcutaneously implanted (which is not relevant to septic patients), this indicates the occurrence of a major immunosuppressive state induced by sepsis and driven by Tregs in this model.

Collectively, and beyond Tregs (unfortunately not the sole bad guys in the game), these data highlight the profound impact of sepsis/injury on immune functions. This should stimulate basic research and development of innovative therapies for rebalancing immune homeostasis in severe critical illness.

Abbreviations

CLP:

cecal ligation and puncture

Treg:

regulatory T cell.

References

  1. 1.

    Christaki E, Patrozou E: The kinetics of T regulatory cells in shock: beyond sepsis. Crit Care. 2010, 14: 132-10.1186/cc8897.

    PubMed Central  Article  PubMed  Google Scholar 

  2. 2.

    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/s00134-008-1337-8.

    PubMed Central  Article  PubMed  Google Scholar 

  3. 3.

    Nascimento DC, Alves-Filho JC, Sônego F, Fukada SY, Pereira MS, Benjamim C, Zamboni DS, Silva JS, Cunha FQ: Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis. Crit Care Med. 2010, 38: 1718-1725. 10.1097/CCM.0b013e3181e78ad0.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Cavassani KA, Carson WF, Moreira AP, Wen H, Schaller MA, Ishii M, Lindell DM, Dou Y, Lukacs NW, Keshamouni VG, Hogaboam CM, Kunkel SL: The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. Blood. 2010, 115: 4403-4411. 10.1182/blood-2009-09-241083.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Guillaume Monneret.

Additional information

Competing interests

The authors declare that they have no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Monneret, G., Venet, F. Additional bad news from regulatory T cells in sepsis. Crit Care 14, 453 (2010). https://doi.org/10.1186/cc9357

Download citation

Keywords

  • Critical Illness
  • Septic Patient
  • Septic Shock Patient
  • Cecal Ligation
  • Immune Homeostasis