TY - JOUR
T1 - Overexpression of interleukin-15 increases susceptibility to lipopolysaccharide-induced liver injury in mice primed with Mycobacterium bovis bacillus Calmette-Guérin
AU - Yajima, Toshiki
AU - Nishimura, Hitoshi
AU - Saito, Kimika
AU - Kuwano, Hiroyuki
AU - Yoshikai, Yasunobu
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
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U2 - 10.1128/IAI.72.7.3855-3862.2004
DO - 10.1128/IAI.72.7.3855-3862.2004
M3 - Article
C2 - 15213127
AN - SCOPUS:3042588577
SN - 0019-9567
VL - 72
SP - 3855
EP - 3862
JO - Infection and Immunity
JF - Infection and Immunity
IS - 7
ER -
