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 alpha beta T lymphocytes; however, the role of gamma delta T lymphocytes in the immune response after thermal injury is unclear. Therefore, wild-type mice and mice lacking the TCR delta gene (TCR delta(-/-)) were subjected to a third-degree scald burn and cell-mediated immune responses assessed at 7 days post-injury. TCR delta(-/-) mice had 75% mortality after burn injury compared with 25% mortality in the wild-type group, Plasma interluekin-6 (IL-6) levels were significantly elevated at 2, 4, and 18 h post-injury, whereas no difference was observed in tumor necrosis factor cc (TNF-alpha) and prostaglandin E-2 (PGE(2)) plasma levels. Plasma levels of these inflammatory mediators were similar in wild-type and TCR delta(-/-) mice post-injury, Splenic macrophage PGE2, IL-6, TNF-alpha, and IL-10 production was significantly increased in wild-type mice at 7 days post-injury, whereas macrophages from injured TCR delta(-/-) mice had a significantly attenuated capacity to produce IL-6 and TNF-alpha. In contrast, the increased release of PGE2 and IL-10 by macrophages post-injury was not reduced in TCR delta(-/-) mice. These results implicate a dual role for gamma delta 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, gamma delta T lymphocytes, in part through the modulation of macrophage activity, appear to contribute to the immune dysfunction after thermal injury.