Background. The mechanisms responsible for altered T-cell responses and cytokine production after injury are not well understood. We used T-cell receptor (TCR) transgenic mice to study burn injury effects on naive versus antigen-activated CD4+ T cells in vivo. Methods. One week after sham or burn injury, lymph node cells were prepared from TCR transgenic mice and stimulated with TCR transgene-specific antigens. T-cell proliferation was measured and culture supernatants were tested for interleukin-2 (IL-2), interferon-γ (IFN-γ), IL-4, and IL-10 by enzyme-linked immunosorbent assay (ELISA). Burn injury effects on antigen-activated T cells were studied by immunizing TCR transgenic or wild-type mice at the time of injury. Results. The antigen-stimulated proliferation of naive CD4+ T cells was unaffected by burn injury and no increase in T-helper 2 (Th2)-type cytokine production was observed. Instead, burn injury augmented IFN-γ production by naive CD4+ transgenic T cells, and IL-2 production was marginally reduced. Thus, burn injury primed naive T cells for an enhanced Th1-type response. In contrast, antigen-specific protiferation, IL-2, and IFN-γ production by T cells harvested from immunized wild-type mice were suppressed. Unexpectedly, high mortality was observed when burn-injured TCR transgenic mice were immunized. Conclusion. Our results show that burn injury has differential effects on naive and antigen-activated CD4+ T cells and can prime naive CD4+ T cells.
Bibliographical noteFunding Information:
Supported in part by NIH grant GM775033 and by the Julian and Eunice Cohen and David Brook Funds for Surgical Research. Eamon Kavanagh and John Kelly were supported in part by the Ainsworth Scholarship, University College, Cork, Ireland.
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