Overexpression of interleukin-15 increases susceptibility to lipopolysaccharide-induced liver injury in mice primed with Mycobacterium bovis bacillus Calmette-Guérin

Toshiki Yajima, Hitoshi Nishimura, Kimika Saito, Hiroyuki Kuwano, Yasunobu Yoshikai

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    Abstract

    Mice primed with Mycobacterium bovis bacillus Calmette-Guérin (BCG) are highly sensitive to lipopolysaccharide (LPS)-induced liver injury and lethality. We found that interleukin-15 (IL-15) transgenic (Tg) mice primed with BCG were more susceptible to LPS-induced liver injury than non-Tg mice. The numbers of CD44+ CD8+ T cells expressing intracellular gamma interferon (IFN-γ) significantly increased in the livers of BCG-primed IL-15 Tg mice after LPS injection, and the depletion of CD8 + T cells from BCG-primed IL-15 Tg mice completely abolished the susceptibility to LPS-induced lethality. Liver T cells from BCG-primed IL-15 Tg mice produced IFN-γ in vitro in response to LPS, which was inhibited by the addition of anti-IL-12 monoclonal antibody (MAb). In vivo treatment with anti-IL-12 MAb inhibited the appearance of CD44+ CD8+ T cells expressing intracellular IFN-γ after LPS injection. These results suggest that the overexpression of IL-15 increases susceptibility to LPS-induced liver injury in BCG-primed mice via bystander activation of CD8+ T cells.

    Original languageEnglish
    Pages (from-to)3855-3862
    Number of pages8
    JournalInfection and Immunity
    Volume72
    Issue number7
    DOIs
    Publication statusPublished - Jul 1 2004

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    All Science Journal Classification (ASJC) codes

    • Parasitology
    • Microbiology
    • Immunology
    • Infectious Diseases

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