Injury primes the immune system for an enhanced and lethal T-cell responseagainst bacterial superantigen

We previously reported the high lethality of CD4+ T-cell activation in burn -injured T-cell receptor (TCR) transgenic mice. This suggested to us that T -cells may play a role in the development of the systemic inflammatory resp onse syndrome (SIRS) which can occur after severe injury. In this study, we sought a more clinically relevant model to test the hypothesis that natura lly produced bacterial toxins that are known to act as potent polyclonal T- cell activating agents may induce a similar lethal shock-like response in i njured, non-TCR transgenic mice. Accordingly, sham- or burn-injured mice we re treated with various doses of staphylococcal enterotoxin A (SEA), then o bserved for 48-hour mortality. We observed 94% and 56% 48-h mortality when burn-injured mice were given 15 mu g and 10 mu g of SEA, respectively, whil e neither SEA dose caused mortality in sham-injured mice. The assessment of serum cytokine levels demonstrated significantly elevated interleukin 2 (I L-2) and tumor necrosis factor alpha (TNF alpha) levels when compared to sh am mice (P < 0.01). In vitro studies confirmed our in vivo results and also demonstrated elevated levels of interferon gamma (IFN gamma) (P < 0.01). W e also observed a novel injury-dependent switch from CD4+ to CD8+ T-cells a s the dominant T-cell type producing TNF alpha and IFN gamma in response to SEA stimulation in vitro. Taken together, our findings indicate that injur y primes the immune system for an augmented early T-cell response that can result in a lethal shock-like syndrome.