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Published online before print December 6, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0707507

Received for publication July 30, 2007.
Revised October 19, 2007.
Accepted for publication October 31, 2007.

Article

T cells mitigate the organ injury and mortality of sepsis

Johannes Tschöp ^*, André Martignoni ^*, Holly S. Goetzman ^*, Lisa G. Choi ^*, Quan Wang , John G. Noel , Cora K. Ogle ^*, Timothy A. Pritts ^*, Jay A. Johannigman ^*, Alex B. Lentsch ^*, and Charles C. Caldwell ^*@

*The Laboratory of Trauma, Sepsis & Inflammation Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; Department of Research, Shriner’s Hospital for Children (SHC), Cincinnati, Ohio, USA; and Department of Anesthesiology, Klinikum Grosshadern, Munich, Germany

^@ To whom correspondence should be addressed. E-mail: charles.caldwell{at}uc.edu.

	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. T cells are found largely in epithelial-rich tissues, and previous studies of T cells in models of sepsis have yielded divergent results. In the present study, we examined the function of T cells during sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in T cells had decreased survival times and increased tissue damage after CLP compared with wild-type mice. Furthermore, bacterial load was increased in 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 T cell-deficient mice. Finally, we found that circulating levels of IFN- were increased, and systemic levels of IL-10 were decreased in T cell-deficient mice after CLP compared with wild-type mice. T cell-deficient mice also had increased intestinal permeability after CLP compared with wild-type mice. Neutralization of IFN- abrogated the increase in intestinal permeability in T cell-deficient mice. The intestines taken from T cell-deficient mice had decreased myeloperoxidase yet had increased tissue damage as compared with wild-type mice. Collectively, our data suggest that T cells modulate the response to sepsis and may be a potential therapeutic target.

Key Words: IFN- • intestine • myeloid suppressor cells • neutrophils • bacteremia