Lung mucosal and systemic responses at single-cell resolution in an aerosolised Mycobacterium bovis BCG human challenge model

Pre-existing BCG-expanded TCR clones were more likely to be activated CD4⁺ T cells and were more enriched in the lung mucosa than newly expanded TCR clones. Only a small proportion of mycobacterial antigen-reactive TCR clones in the blood, detected by the activation-induced marker assay, were enriched in the lung mucosa. Several public BCG-expanded TCR clones across individuals were identified in the lung mucosa and shown to be reactive to mycobacterial antigens using artificial antigen-presenting cells and reporter T cells.

Overall, our study provides crucial insights into the dynamics of human mucosal and systemic immunity following aerosolised BCG challenge, informing the design of more effective TB vaccines.