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 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 α (TNF‐α) and prostaglandin E 2 (PGE 2 ) plasma levels. Plasma levels of these inflammatory mediators were similar in wild‐type and TCR δ −/‐_ mice post‐injury. Splenic macrophage PGE 2 , 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 PGE 2 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. J. Leukoc. Biol. 67: 644–650; 2000.