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The Journal of Immunology, 2001, 167: 946-956.
Copyright © 2001 by The American Association of Immunologists

Overexpression of IL-15 In Vivo Enhances Protection Against Mycobacterium bovis Bacillus Calmette-Guérin Infection Via Augmentation of NK and T Cytotoxic 1 Responses1

Masayuki Umemura*, Hitoshi Nishimura*, Kenji Hirose{dagger}, Tetsuya Matsuguchi* and Yasunobu Yoshikai2,*

* Laboratory of Host Defense, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan; and {dagger} Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan

To investigate the immunomodulating effects of IL-15 in vivo on mycobacterial infection, we used IL-15-transgenic (Tg) mice, which were recently constructed with cDNA-encoding secretable isoform of IL-15 precursor protein under the control of a MHC class I promoter. The IL-15-Tg mice exhibited resistance against infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG), as assessed by bacteria growth. IFN-{gamma} level in serum was significantly higher in IL-15-Tg mice than in non-Tg mice after BCG infection. NK cells were remarkably increased, and Ag-specific T cytotoxic 1 response mediated by CD8+ T cells producing IFN-{gamma} was significantly augmented in the IL-15-Tg mice following BCG infection. Neutralization of endogenous IFN-{gamma} by in vivo administration of anti-IFN-{gamma} mAb deteriorated the clearance of the bacteria. Depletion of of NK cells or CD8+ T cells by invivo administration of anti-asialo-GM1 Ab or anti-CD8 mAb hampered the exclusion of bacteria. Thus, overexpression of IL-15 in vivo enhanced protection against BCG infection via augmentation of NK and T cytotoxic 1 responses.




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