Volume 11 Supplement 4

Sepsis 2007

Open Access

The role of regulatory T cells in the resistance of CCR4 knockout mice during severe sepsis

  • Raphael Molinaro1,
  • Alessandra Monteiro de França1,
  • Josi Alves-Filho2,
  • Fernando de Queiroz Cunha2,
  • Marcelo Bozza3,
  • Steven Kunkel4 and
  • Claudia Benjamim1
Critical Care200711(Suppl 4):P2

https://doi.org/10.1186/cc5981

Published: 26 September 2007

Background

Studies reveal that regulatory T (Treg) cells control immune responses; therefore these responses must be controlled to enable effective protection against infections and cancer. CCR4 knockout (CCR4-/-) mice are more resistant to lipopolysaccharide shock. So, our aim is to study the mechanisms involved in the resistance of CCR4-/- mice subjected to severe sepsis by cecal ligation and puncture (CLP) and how Treg cells modulate this effect.

Methods

C57/BL6 mice were subjected to a CLP model, whereby the cecum was partially ligated and punctured nine times with a 21 G needle. Sham-operated mice were used as control. Mice subjected to CLP and sham surgery were treated with antibiotic from 6 hours after surgery until 3 days.

Results

CCR4-/- mice subjected to CLP presented an increase in the survival rate (78%) compared with wild-type mice (17%), and presented a marked improvement in the innate response concerning neutrophil migration to the peritoneum and lung, bacterial load and cytokine levels compared with wild-type mice. Besides, Treg cells from CCR4-/- CLP mice did not inhibit proliferation of T effector cells as observed for Treg cells from wild CLP mice, at a proportional ratio of T effector: Treg cells. Interesting, Treg cells from CCR4-/- CLP mice inhibit 30% of neutrophil migration to bronchoalveolar lavage when co-injected with fungal challenge as secondary infection in sham recipient mice, while the cells Treg from wild CLP mice inhibit 80%, much more than expected.

Conclusion

These results suggest that Treg cells from CCR4-/- mice did not present a suppressive response and this could be an important factor in their survival. These results are strong evidence for the role of Treg cells in immunosuppression following severe sepsis.

Authors’ Affiliations

(1)
Department of Pharmacology, UFRJ
(2)
Department of Pharmacology, USP
(3)
Microbiology Institute, UFRJ
(4)
Department of Pathology, UMMS

Copyright

© BioMed Central Ltd 2007

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