Antigen-experienced airway CD8 effector memory T cells promote a detour pathway for mycobacterial killing in the spleen
Seifert, Julia, Muruganandah, Visai, Miranda-Hernandez, Socorro, Sathkumara, Harindra D., Valencia-Hernandez, Ana Maria, Pai, Saparna, and Kupz, Andreas (2026) Antigen-experienced airway CD8 effector memory T cells promote a detour pathway for mycobacterial killing in the spleen. Science Advances, 12 (34). eaec7792.
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Abstract
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.
| Item ID: | 93793 |
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| Item Type: | Article (Refereed Research - C1) |
| ISSN: | 2375-2548 |
| Copyright Information: | Copyright © 2026 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). |
| Date Deposited: | 26 Aug 2026 06:56 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320702 Medical infection agents (incl. prions) @ 100% |
| SEO Codes: | 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100% |
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