Gamma delta (γδ) T-cells are critical in the up-regulation of inducible nitric oxide synthase at the burn wound site

Background: The high incidence of morbidity and mortality following major burn can in part be attributed to immune derangements and wound healing complications. Inflammation plays an important role in wound healing, of which inducible nitric oxide synthase (iNOS) derived nitric oxide is a central mediator. T-cells of the gamma delta TCR lineage have also been shown to be important in healing of the burn wound site. Nonetheless, the role of gamma delta T-cells in the regulation of the burn wound iNOS expression is unknown. Methods: Wildtype (WT) and delta TCR-/- male C57BL/6 mice were subjected to burn (3rd degree, 12.5% TBSA) or sham treatment. Three days after injury, skin samples from non-injured and the burn wound were collected and analyzed for the expression of iNOS and cytokines and chemokine levels. In a second series of experiments, WT mice were subjected to burn and left untreated or treated with the iNOS inhibitor, L-Nil. Skin cytokine and chemokine levels were assessed 3 days thereafter. Results: Burn induced an 18-fold increase in iNOS expression at the wound site as compared to the uninjured skin of WT sham mice. In delta TCR-/- mice iNOS expression at the wound site was significantly lower than that of the WT group. Burn also induced increased levels of IL-1 beta, IL-6, G-CSF, TNF-alpha, KC, MCP-1, MIP-1 alpha and MIP-1 beta at the wound site in WT and delta TCR-/- mice, but G-CSF, TNF-alpha, and MIP-1 beta levels were greater in delta TCR-/- mice. Inhibition of iNOS activity in WT mice with L-Nil suppressed burn wound levels of IL-1 beta, G-CSF, and MIP-1 alpha, whereas IL-6, TNF-alpha, KC, MCP-1 and MIP-1 beta were unaffected. Conclusions: T-cells of the gamma delta TCR lineage significantly contribute to the up-regulation of iNOS expression which contributes to wound inflammation. (C) 2012 Elsevier Ltd. All rights reserved.