The role of gammadelta T cells in the regulation of neutrophil-mediated tissue damage after thermal injury.
Thermal injury induces an inflammatory response that contributes to the development of secondary tissue damage. Neutrophil recruitment and activation are in part responsible for this tissue damage. Although gammadelta T cells have been shown to regulate the inflammatory responses in tissues that are prone to neutrophil-mediated injury post-burn, their role in the induction of secondary tissue injury post-burn remains unknown. To study this, gammadelta T cell-deficient (gammadelta TCR-/-) and wild-type (WT) mice were subjected to thermal injury or sham procedure, and tissue samples were isolated 1-24 h thereafter. Burn injury induced neutrophil accumulation in the lung and small intestines of WT mice at 1-3 h post-injury. No such increase in neutrophil tissue content was observed in gammadelta TCR-/- mice. An increase in tissue wet/dry weight ratios was also observed in these organs at 3 h post-burn in WT but not in gammadelta TCR-/- mice. A parallel increase in plasma and small intestine levels of the chemokines macrophage-inflammatory protein-1beta (chemokine ligand 4) and keratinocyte-derived chemokine (CXC chemokine ligand 1) were observed in injured WT mice but not in injured gammadelta TCR-/- mice. Increased activation (CD120b expression) of the circulating gammadelta T cell population was also observed at 3 h post-burn in WT mice. These results indicate the gammadelta T cells, through the production of chemokines, play a central role in the initiation of neutrophil-mediated tissue damage post-burn.
Toth
Balazs
B
Center for Surgical Research, Department of Surgery, G094 Volker Hall, 1670 University Blvd., Birmingham, AL 35294-0019, USA.
Alexander
Michelle
M
Daniel
TanJanika
T
Chaudry
Irshad H
IH
Hubbard
William J
WJ
Schwacha
Martin G
MG
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002056:Burns / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000276:immunology / Q000503:physiopathology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D023062:Receptors, Interleukin-8A / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023062:Receptors, Interleukin-8A; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II