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Production in the Generalized Shwartzman Reaction
*
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan;
Department of Immunology, Faculty of Medicine, University of Tokyo, and
Department of Immunology, Juntendo University School of Medicine, Bunkyou-ku, Tokyo, Japan;
§
Second Department of Oral Surgery, Tohoku University School of Dentistry,
¶
First Department of Surgery and
||
Department of Dermatology, Tohoku University School of Medicine, and
#
Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; and
**
Division of Basic Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan
IL-12 (or LPS) priming and subsequent challenge by LPS produces the
generalized Shwartzman reaction. IFN-
induced by IL-12 is a crucial
cytokine in the priming phase. In vivo depletion of both NK cells and
NK1+ 
ß T cells of mice by anti-NK1.1 Ab
greatly reduced the elevation of serum IFN- induced by IL-12 and
significantly reduced mortality after subsequent injection of LPS,
whereas depletion of NK cells alone by anti-asialo GM1 Ab only
partially decreased serum IFN-, and lethality was not changed. Cell
sorting and culture experiments confirmed that liver NK1+
ß T cells of IL-12-injected mice produced greater amounts of
IFN- than did liver NK cells. MHC class I-deficient mice of C57BL/6
background, which lack a majority of NK1+ ß T cells,
produced low amounts of IFN- by IL-12; no mortality was observed
after the LPS challenge. However, production of TNF- in the second
phase (after LPS challenge) was not inhibited by depletion of NK cells
alone or both subsets. IL-12 and subsequent LPS challenge activated
NK1+ ß T cells in the liver and induced strong
cytotoxicity of these cells not only against tumor cells (including
Fas-negative tumors) but also against a syngeneic hepatocyte cell line.
Our findings show that IFN- produced by NK1+ ß T
cells is essential for the IL-12 priming of the Shwartzman reaction,
and the autoreactivity of NK1+ ß T cells in the liver
is involved in the hepatic disorders that are sometimes caused by
IL-12, LPS, or the generalized Shwartzman reaction.
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