A central role for CD95 (Fas) in T-cell reactivity after injury

Background. Recent findings indicate that severe injury primes the immune system for nn enhanced and lethal proinflammatory cytokine response against bacterial-derived superantigens. This study asked whether this response to injury involves the CD95 (Fas) signaling pathway. Methods. To assess superantigen-mediated mortality wild-type (WT) C57BL/6 and Fns-deficient C57BL/6 lpr (-/-) (lpr) mice underwent burn or sham injury and were challenged 2 hours later with staphylococcal enterotoxin B (SEB). Spleen cells from sham and burn WT or lpr mice were stimulated in vitro with SEE to assess injury effects on IL-2 TNF-alpha, and IFN-gamma production. Results. Lpr burn mice survived the SEB challenge (100% survival), while WT burn mice showed a high mortality (17% survival, P <001, analysis of variance [ANOVA]). Sham lpr or WT mice suffered no mortality to the SEE challenge. In vitro studies demonstrated that burn lpr mice produced significantly less TNF-alpha, IFN-gamma, IL-2 than burn WT mice (P <.01, ANOVA. Burn injury markedly enhanced SEB-stimulated IFN-gamma production by WT spleen cells and CD8+ T cells, while this did not occur in SEB-stimulated lpr spleen cells. Conclusions. These findings support the hypothesis that the CD95 (Fas) signaling pathway plays an integral role in the injury-induced enhanced and lethal T-cell reactivity against bacterial superantigens.