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

Authors

Julia Seifert, Visai Muruganandah, Socorro Miranda-Hernandez, Harindra D Sathkumara, Ana Maria Valencia-Hernandez, Saparna Pai, Andreas Kupz

Published in

Science advances. Volume 12. Issue 34. Pages eaec7792. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

A 3-week delay in the onset of T cell immunity to Mycobacterium tuberculosis (Mtb) infection compromises lung bacterial control, resulting in tuberculosis (TB). Restoring T cell function is a priority. We identified how airway CD44⁺CD62L^-KLRG1⁺CD8⁺ effector memory T cells (T_EM) 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_EM versus primary. Paradoxically, lower numbers correlated with faster bacterial clearance, due to enhanced trafficking of secondary T_EM to the spleen, where they responded to antigen. Further, secondary T_EM recruited dendritic cells, which accelerated bacterial translocation from the lung to the spleen. Treating mice with a threshold number of airway-derived secondary T_EM significantly reduced Mtb burden in the lung and spleen. Notably, Mtb killing was expedited by at least 15 days. Repeated antigen encounter bypassed priming requirements and enhanced T_EM durability, uncovering a spleen-centered protective mechanism with implications for improved TB vaccines and therapies.

PMID:
42627884
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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