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

To investigate the immunomodulating effects of IL-15 in vivo on mycobacteri al infection, we used IL-15-transgenic (Tg) mice, which were recently const ructed with eDNA-encoding secretable isoform of IL-15 precursor protein und er the control of a MHC class I promoter. The IL-15-Tg mice exhibited resis tance against infection with Mycobacterium bovis bacillus Calmette-Guerin ( BCG), as assessed by bacteria growth. IFN-gamma level in serum was signific antly higher in IL-15-Tg mice than in non-Tg mice after BCG infection. NK c ells were remarkably increased, and Ag-specific T cytotoxic 1 response medi ated by CD8(+) T cells producing IFN-gamma was significantly augmented in t he IL-15-Tg mice following BCG infection. Neutralization of endogenous IFN- gamma by in vivo administration of anti-IFN-gamma mAb deteriorated the clea rance of the bacteria. Depletion of of NK cells or CD8(+) T cells by in viv o administration of anti-asialo-GM(1) Ab or anti-CD8 mAb hampered the exclu sion of bacteria. Thus, overexpression of IL-15 in vivo enhanced protection against BCG infection via augmentation of NK and T cytotoxic 1 responses.