γδ T cells mitigate the organ injury and mortality of sepsis

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