Antigen-experienced airway CD8 effector memory T cells promote a detour pathway for mycobacterial killing in the spleen

A 3-week delay in the onset of T cell immunity to () infection compromises lung bacterial control, resulting in tuberculosis (TB). Restoring T cell function is a priority. We identified how airway CD44CD62LKLRG1CD8 effector memory T cells (T) in the lung enhance mycobacterial clearance via the spleen. Unexpectedly, a secondary immune response following repeated exposure of mice to Bacille Calmette-Guérin generated lower numbers of T versus primary. Paradoxically, lower numbers correlated with faster bacterial clearance, due to enhanced trafficking of secondary T to the spleen, where they responded to antigen. Further, secondary T recruited dendritic cells, which accelerated bacterial translocation from the lung to the spleen. Treating mice with a threshold number of airway-derived secondary T significantly reduced burden in the lung and spleen. Notably, killing was expedited by at least 15 days. Repeated antigen encounter bypassed priming requirements and enhanced T durability, uncovering a spleen-centered protective mechanism with implications for improved TB vaccines and therapies.

Science Advances

Science Advances

12

2375-2548

N/A

34

16