Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis bacillus Calmette-Guérin infection via augmentation of NK and T cytotoxic 1 responses

M. Umemura, H. Nishimura, K. Hirose, T. Matsuguchi, Yasunobu Yoshikai

    Research output: Contribution to journalArticle

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    Abstract

    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-γ 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-γ was significantly augmented in the IL-15-Tg mice following BCG infection. Neutralization of endogenous IFN-γ by in vivo administration of anti-IFN-γ mAb deteriorated the clearance of the bacteria. Depletion of NK cells or CD8+ T cells by in vivo 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.

    Original languageEnglish
    Pages (from-to)946-956
    Number of pages11
    JournalJournal of Immunology
    Volume167
    Issue number2
    DOIs
    Publication statusPublished - Jul 15 2001

    Fingerprint

    Interleukin-15
    Mycobacterium bovis
    Bacillus
    Transgenic Mice
    Infection
    Bacteria
    Natural Killer Cells
    T-Lymphocytes
    Protein Precursors
    Protein Isoforms
    Complementary DNA
    Growth
    Serum

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis bacillus Calmette-Guérin infection via augmentation of NK and T cytotoxic 1 responses. / Umemura, M.; Nishimura, H.; Hirose, K.; Matsuguchi, T.; Yoshikai, Yasunobu.

    In: Journal of Immunology, Vol. 167, No. 2, 15.07.2001, p. 946-956.

    Research output: Contribution to journalArticle

    Umemura, M. ; Nishimura, H. ; Hirose, K. ; Matsuguchi, T. ; Yoshikai, Yasunobu. / Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis bacillus Calmette-Guérin infection via augmentation of NK and T cytotoxic 1 responses. In: Journal of Immunology. 2001 ; Vol. 167, No. 2. pp. 946-956.
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    abstract = "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. Gu{\'e}rin (BCG), as assessed by bacteria growth. IFN-γ 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-γ was significantly augmented in the IL-15-Tg mice following BCG infection. Neutralization of endogenous IFN-γ by in vivo administration of anti-IFN-γ mAb deteriorated the clearance of the bacteria. Depletion of NK cells or CD8+ T cells by in vivo 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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