Involvement of NK1+ T cells and their IFN-γ production in the generalized Shwartzman reaction

Koetsu Ogasawara, Kazuyoshi Takeda, Wataru Hashimoto, Masayuki Satoh, Ryuhei Okuyama, Nobuaki Yanai, Masuo Obinata, Katsuo Kumagai, Haruhiko Takada, Hoshio Hiraide, Shuhji Seki

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

IL-12 (or LPS) priming and subsequent challenge by LPS produces the generalized Shwartzman reaction. IFN-γ induced by IL-12 is a crucial cytokine in the priming phase. In vivo depletion of both NK cells and NK1+ αβT cells of mice by anti-NK1.1 Ab greatly reduced the elevation of serum IFN-γ 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-τ, and lethality was not changed. Cell sorting and culture experiments confirmed that liver NK1+ αβ T cells of IL-12-injected mice produced greater amounts of IFN-γ than did liver NK cells. MHC class I-deficient mice of C57BL/6 background, which lack a majority of NK1+ αβ T cells, produced low amounts of IFN-γ by IL-12; no mortality was observed after the LPS challenge. However, production of TNF- α in the second phase (after LPS challenge) was not inhibiter by depletion of NK cells alone or both subsets. IL-12 and subsequent LPS challenge activated NK1+ αβ 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-γ produced by NK1+ αβ T cells is essential for the IL-12 priming of the Shwartzman reaction, and the outoreactivity of NK1+ αβ T cells in the liver is involved in the hepatic disorders that are sometimes caused by IL- 12, LPS, or the generalized Shwartzman reaction.

Original languageEnglish
Pages (from-to)3522-3527
Number of pages6
JournalJournal of Immunology
Volume160
Issue number7
Publication statusPublished - 1998 Apr 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Involvement of NK1<sup>+</sup> T cells and their IFN-γ production in the generalized Shwartzman reaction'. Together they form a unique fingerprint.

Cite this