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Published online before print December 6, 2007

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(Journal of Leukocyte Biology. 2008;83:581-588.)
© 2008 by Society for Leukocyte Biology

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^*,,1

^* The Laboratory of Trauma, Sepsis and 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

¹Correspondence: University of Cincinnati College of Medicine, 231 Albert Sabin Way, MSB SRU G479 ML 0558, Cincinnati, OH 45267-0558, USA. 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