Insights into the role of γδ T lymphocytes in the immunopathogenic response to thermal injury

Studies have shown that cell-mediated immunity is markedly suppressed after thermal injury. T lymphocyte dysfunction and macrophage hyperactivity have been implicated as causative factors. Previous studies have primarily examined the effects of thermal injury on αβ T lymphocytes; however, the role of γδ T lymphocytes in the immune response after thermal injury is unclear. Therefore, wild-type mice and mice lacking the TCR δ gene (TCR δ(-/-) were subjected to a third-degree scald burn and cell-mediated immune responses assessed at 7 days post-injury. TCR δ(-/-) mice had 75% mortality after burn injury compared with 25% mortality in the wild-type group. Plasma interleukin-6 (IL-6) levels were significantly elevated at 2, 4, and 18 h post-injury, whereas no difference was observed in tumor necrosis factor α (TNF-α) and prostaglandin E₂ (PGE₂) plasma levels. Plasma levels of these inflammatory mediators were similar in wild-type and TCR δ(-/-) mice post-injury. Splemic macrophage PGE₂, IL-6, TNF-α, and IL-10 production was significantly increased in wild-type mice at 7 days post-injury, whereas macrophages from injured TCR δ(-/-) mice had a significantly attenuated capacity to produce IL-6 and TNF-α. In contrast, the increased release of PGE₂ and IL-10 by macrophages post-injury was not reduced in TCR δ(-/-) mice. These results implicate a dual role for γδ T lymphocytes in the immunopathogenic response to burn injury: (1) they contribute to survival from the insult; and (2) they mediate the induction of a pro-inflammatory macrophage phenotype at 7 days post-injury, Thus, γδ T lymphocytes, in part through the modulation of macrophage activity, appear to contribute to the immune dysfunction after thermal injury.