Gammadelta 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. 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.
Tschöp
Johannes
J
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.
Martignoni
André
A
Goetzman
Holly S
HS
Choi
Lisa G
LG
Wang
Quan
Q
Noel
John G
JG
Ogle
Cora K
CK
Pritts
Timothy A
TA
Johannigman
Jay A
JA
Lentsch
Alex B
AB
Caldwell
Charles C
CC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007422:Intestines / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012016:Reference Values; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014949:Wounds, Nonpenetrating / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control
D016692:Receptors, Antigen, T-Cell, gamma-delta