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J Leukoc Biol. 2008 Mar;83(3):581-8. Epub 2007 Dec 6.

Gammadelta T cells mitigate the organ injury and mortality of sepsis.

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1
The Laboratory of Trauma, Sepsis and Inflammation Research, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA.

Abstract

Sepsis is a difficult condition to treat and is associated with a high mortality rate. Sepsis is known to cause a marked depletion of lymphocytes, although the function of different lymphocyte subsets in the response to sepsis is unclear. gammadelta T cells are found largely in epithelial-rich tissues, and previous studies of gammadelta T cells in models of sepsis have yielded divergent results. In the present study, we examined the function of gammadelta T cells during sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in gammadelta T cells had decreased survival times and increased tissue damage after CLP compared with wild-type mice. Furthermore, bacterial load was increased in gammadelta T cell-deficient mice, yet antibiotic treatment did not change mortality. Additionally, we found that recruitment of neutrophils and myeloid suppressor cells to the site of infection was diminished in gammadelta T cell-deficient mice. Finally, we found that circulating levels of IFN-gamma were increased, and systemic levels of IL-10 were decreased in gammadelta T cell-deficient mice after CLP compared with wild-type mice. gammadelta T cell-deficient mice also had increased intestinal permeability after CLP compared with wild-type mice. Neutralization of IFN-gamma abrogated the increase in intestinal permeability in gammadelta T cell-deficient mice. The intestines taken from gammadelta T cell-deficient mice had decreased myeloperoxidase yet had increased tissue damage as compared with wild-type mice. Collectively, our data suggest that gammadelta T cells modulate the response to sepsis and may be a potential therapeutic target.

PMID:
18063696
PMCID:
PMC2747639
DOI:
10.1189/jlb.0707507
[Indexed for MEDLINE]
Free PMC Article
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