LPS induces NK1.1+ αβ T cells with potent cytotoxicity in the liver of mice via production of IL-12 from Kupffer cells

Motoyoshi Takahashi, Kouetsu Ogasawara, Kazuyoshi Takeda, Wataru Hashimoto, Hiroshi Sakihara, Katsuo Kumagai, Ryoichi Anzai, Masayuki Satoh, Shuhji Seki

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131 Citations (Scopus)


We recently reported that systemic administration of IL-12 into mice activates NK1.1+ αβ T cells with intermediate TCR (NK1+TCR(int)) and induces strong MHC-unrestricted cytotoxicity in C57BL/6 mice. In the present report, we examined the effect of LPS on Kupffer cells and NK1+TCR(int) cells in C57BL/6 mice. Administration of LPS, as well as synthetic lipid A analogue (ONO-4007), but not detoxified LPS, induces the increase of NK1 expression of NKI+TCR(int) cells (NK1(high)TCR(int)) and the acquisition of strong MHC-unrestricted cytotoxicity of these cells against NK-sensitive and NK-resistant targets as does IL-12 administration. LPS as well as ONO-4007 induced IL-12 mRNA in hepatic mononuclear cells, mainly in plastic-adherent Kupffer cells. LPS-induced cytotoxicity of hepatic mononuclear cells was greatly reduced by in vivo injections of anti-IL-12 Ab, to a lesser extent by anti-IFN-γ Ab, but not by anti-IL-1 nor anti-TNF-α Ab. Pretreatment of mice with LPS induced inhibition of hepatic metastases of i.v. injected EL4 cells in C57BL/6 euthymic and athymic mice and this antimetastasis was inhibited by injection of anti-IL-12 Ab. This antimetastatic effect of LPS in the liver was also observed in different strains of mice and tumors. In contrast to IL- 12, however, LPS was not so effective when administered after tumor inoculation. These results revealed that LPS (lipid A) stimulates NK1+TCR(int) cells through IL-12 production from Kupffer cells and suggest that bacterial components, probably including those from intestine, are activators of Kupffer cells and NK1+TCR(int) cells in the liver. It is also suggested that the host condition as well as LPS-induced cytokines other than IL-12 may affect antitumor effect induced by LPS in the liver.

Original languageEnglish
Pages (from-to)2436-2442
Number of pages7
JournalJournal of Immunology
Issue number7
Publication statusPublished - 1996 Apr 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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