The role of γδ 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 γδ 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, γδ T cell-deficient (γδ 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 γδ 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 γδ TCR^-/- mice. A parallel increase in plasma and small intestine levels of the chemokines macrophage-inflammalory protein-1β (chemokine ligand 4) and keratinocyte-derived chemokine (CXC chemokine ligand 1) were observed in injured WT mice but not in injured γδ TCR^-/- mice. Increased activation (CB120b expression) of the circulating γδ T cell population was also observed at 3 h post-burn in WT mice. These results indicate the γδ T cells, through the production of chemokines, play a central role in the initiation of neutrophil-mediated tissue damage post-burn.