The Journal of Experimental Medicine
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Published online 4 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1645/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1645-1652

Brief Definitive Report

Resistance of Natural Killer T Cell–Deficient Mice to Systemic Shwartzman Reaction

Francesco Dielia, Guido Sirecia, Domenica Russob, Masaru Taniguchic, Juraj Ivanyid, Carmen Fernandeze, Marita Troye-Blomberge, Giacomo De Leoa, and Alfredo Salernoa,b

a Department of Biopathology, University of Palermo,
b Institute for Advanced Diagnostic Methodologies, National Research Council, 90134 Palermo, Italy
c Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, Chiba 260-8670, Japan
d King's College London at Guy's Medical and Dental School, London SE1 9RT, United Kingdom
e Department of Immunology, Stockholm University, S-106 91 Stockholm, Sweden
Institute of Advanced Diagnostic Methodologies, National Research Council, Corso Tukory, 211, 90134 Palermo, Italy.39-091-655-590139-091-655-5903

asalerno{at}unipa.it

The generalized Shwartzman reaction in mice which had been primed and challenged with lipopolysaccharide (LPS) depends on interleukin (IL)-12–induced interferon (IFN)-{gamma} production at the priming stage. We examined the involvement in the priming 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 genetically deficient mice were found to be resistant to LPS-elicited mortality. This outcome can be attributed to the reduction of IFN-{gamma} production, because 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 cell–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 that the numerically small NKT cell population of normal mice apparently plays a mandatory role in the priming stage of the generalized Shwartzman reaction.

Key Words: natural killer T cells • interferon {gamma} • interleukin 12 • lipopolysaccharide • Shwartzman reaction

© 2000 The Rockefeller University Press


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