This article is part of the supplement: Sepsis 2007
The role of regulatory T cells in the resistance of CCR4 knockout mice during severe sepsis
1 Department of Pharmacology, UFRJ, Rio de Janeiro, RJ, Brazil
2 Department of Pharmacology, USP, Ribeirão Preto, SP, Brazil
3 Microbiology Institute, UFRJ, Rio de Janeiro, RJ, Brazil
4 Department of Pathology, UMMS, Ann Arbor, MI, USA
Critical Care 2007, 11(Suppl 4):P2 doi:10.1186/cc5981
The electronic version of this article is the complete one and can be found online at: http://ccforum.com/content/11/S4/P2
| Published: | 26 September 2007 |
© 2007 BioMed Central Ltd
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.