Airway luminal T cells: A newcomer on the stage of TB vaccination strategies

Protection against pulmonary tuberculosis (TB) by vaccination is often ascribed to the presence of TB-reactive T cells in the lung before infection. Challenging this view, new studies analyzing vaccine-induced T cells in various tissue compartments after parenteral immunization suggest a poor correlation between the presence of anti-TB T cells in the lung interstitium and spleen before Mycobacterium tuberculosis exposure and protection. In contrast, respiratory mucosal immunization leads to distribution of T cells not only in the lung interstitium and spleen, but also in the airway lumen, and the presence of these cells correlates well with protection. Furthermore, airway luminal recruitment of parenteral vaccine-induced T cells in peripheral tissues prior to M. tuberculosis challenge restores protection. We propose that understanding the biology of airway luminal T cells holds important implications for developing effective TB vaccination strategies.