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Infection and Immunity, July 2004, p. 3855-3862, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3855-3862.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Overexpression of Interleukin-15 Increases Susceptibility to Lipopolysaccharide-Induced Liver Injury in Mice Primed with Mycobacterium bovis Bacillus Calmette-Guérin

Toshiki Yajima,1,2* Hitoshi Nishimura,1 Kimika Saito,1 Hiroyuki Kuwano,2 and Yasunobu Yoshikai1

Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582,1 First Department of Surgery, Gunma University School of Medicine, Maebashi 371-8511, Japan2

Received 17 November 2003/ Returned for modification 5 January 2004/ Accepted 3 March 2004

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.

* Corresponding author. Mailing address: Division of Host Defense, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. Phone: 81-92-642-6962. Fax: 81-92-642-6973. E-mail: yajimato{at}bioreg.kyushu-u.ac.jp.

Editor: J. N. Weiser

Infection and Immunity, July 2004, p. 3855-3862, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3855-3862.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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