Overexpression of Interleukin-15 increases susceptibility to lipopolysaccharide-induced liver injury in mice primed with Mycobacterium bovis bacillus Calmette-Guerin.
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-gamma) 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-gamma 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-gamma 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.
Yajima
Toshiki
T
Division of Host Defense, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. yajimato@bioreg.kyushu-u.ac.jp
Nishimura
Hitoshi
H
Saito
Kimika
K
Kuwano
Hiroyuki
H
Yoshikai
Yasunobu
Y
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000473:pathology*; D051379:Mice; D009163:Mycobacterium bovis / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D019409:Interleukin-15; D008070:Lipopolysaccharides; D007371:Interferon-gamma