Effects of exposure to environmental mycobacteria on immunity conferred by bacille calmette-guerin (BCG) vaccine

Abstract

Epidemiological evidence suggests that the efficacy of Mycobacterium bovis bacille Calmette- Gu??rin (BCG) as a tuberculosis vaccine may be influenced by prior host sensitisation to environmental mycobacteria (Env). This project evaluated the immune mechanisms underlying this phenomenon using a murine model of Mycobacterium chelonae sensitisation followed by intranasal BCG infection. Env sensitisation increased cytotoxicity of splenic T cells against autologous BCG-infected macrophages. This was especially noted at 3 weeks post-infection in the CD4+ fraction, which also contributed largely to the perforin production in those mice. However, the cytotoxicity was not directly correlated with IFN-I? production. Reduced inflammatory cells in the lungs of sensitised mice post-BCG, and a higher proportion of IL-10 producing cells in the lungs suggest induction of regulatory T cells following Env sensitisation. Thus, CD4+ mediated cytotoxicity in Env-primed mice against BCG-infected cells is a mechanism behind the effect of Env exposure on subsequent BCG vaccination.