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

• Published in: The Journal of immunology (1950) Vol. 167; no. 2; pp. 946 - 956
• Main Authors: Umemura, Masayuki, Nishimura, Hitoshi, Hirose, Kenji, Matsuguchi, Tetsuya, Yoshikai, Yasunobu
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2001
• Subjects: Adjuvants, Immunologic - biosynthesis; Adjuvants, Immunologic - genetics; Adjuvants, Immunologic - physiology; Animals; Ascitic Fluid - immunology; Ascitic Fluid - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Cytokines - biosynthesis; Cytokines - blood; Cytotoxicity, Immunologic - immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-15 - biosynthesis; Interleukin-15 - genetics; Interleukin-15 - physiology; Killer Cells, Natural - immunology; Kinetics; Lymphocyte Depletion; Macrophages, Peritoneal - enzymology; Macrophages, Peritoneal - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mycobacterium bovis; Mycobacterium bovis - growth & development; Mycobacterium bovis - immunology; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; RNA, Messenger - biosynthesis; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Tuberculosis - genetics; Tuberculosis - immunology; Tuberculosis - microbiology; Tuberculosis - prevention & control
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.2.946

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 in vivo administration of anti-asialo-GM(1) 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.