Resistance of natural killer T cell-deficient mice to systemic Shwartzman reaction

The generalized Shwartzman reaction in mice which had been primed and chall enged with lipopolysaccharide (LPS) depends on interleukin (IL)-12-induced interferon (IFN)-gamma production at the priming stage. We examined the inv olvement in the printing mechanism of the unique population of V alpha 14, natural killer T (NKT) cells because they promptly produce IFN-gamma after IL-12 stimulation. We report here that LPS- or IL-12-primed NKT cell geneti cally deficient mice were found to be resistant to LPS-elicited mortality. This outcome can be attributed to the reduction of IFN-gamma production, be cause injection of recombinant mouse IFN-gamma, but not injection of IL-12, effectively primed the NKT cell-deficient mice. However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cel l-deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role. These results suggest t hat the numerically small NKT cell population of normal mice apparently pla ys a mandatory role in the priming stage of the generalized Shwartzman reac tion.