A central role for CD95 (Fas) in T-cell reactivity after injury.
BACKGROUND
Recent findings indicate that severe injury primes the immune system for an 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 Fas-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 SEB 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 SEB 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.
Department of Surgery(Immunology), Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
M R
MR
Kell
O
O
Shelley
J A
JA
Mannick
Z
Z
Guo
J A
JA
Lederer
D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000633:toxicity*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D018089:Superantigens / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma