Th17 (IFNγ- IL17+) CD4+ T Cells Generated After Burn Injury May Be a Novel Cellular Mechanism for Postburn Immunosuppression

BACKGROUND: The mechanism responsible for initiating and controlling the immunosuppressive response after burn injury remains unknown. Interleukin-17 (IL-17) secreting Th17 (interferon [IFN]γ IL17) cells are a novel subset of CD4 T cells associated with a weak, proinflammatory response that antagonizes the proinflammatory Th1 (IFNγ IL17) response. Given that transforming growth factor-β and IL6 mediate Th17 cell development, we hypothesized that burn injury may generate Th17 cells that could mediate postburn immunosuppression. METHODS: After a 20% total body surface area burn in female C57BL/6 mice, wound-draining lymph nodes were harvested 3 days, 7 days, or 14 days after injury. CD4 T cells were enriched by magnetic selection, and flow cytometry was used to identify intracellular IL17 and IFNγ in CD3CD4 T cells. Additional purified CD3CD4 T cells were cultured with Th17 polarizing IL6 and transforming growth factor-β for 4 days, and flow cytometry was again used to identify intracellular IL17 and IFNγ in CD4 T cells. RESULTS: The number and percentage of preformed Th17 cells was significantly greater in burn mice compared with sham at all time points. In addition, the ratio of Th17 cells to Th1 cells was always significantly higher in burn mice compared with sham. These differences were eliminated in Th17 polarizing conditions in vitro. CD4 T cells never generated both IL17 and IFNγ. CONCLUSION: These results demonstrate for the first time that Th17 cells (IFNγ IL17) are spontaneously generated after burn injury. Given that Th17 cells (IFNγ IL17) are antagonistic to Th1 (IFNγ IL17) cells, these results suggest a novel mechanism for initiating and controlling postburn immunosuppression that deserves further investigation.