Durability and diversity of human upper airway T cell memory

Ramirez, S. I.; Faraji, F.; Lopez, P. G.; Garin-Ortega, L.; Hern, N. A.; Eisenman, O.; Azhan, A.; Frazier, A.; Phillips, E. J.; Mallal, S.; Sette, A.; Dileepan, T.; Jenkins, M. K.; Crotty, S.

doi:10.64898/2026.09.15.751278

bioRxiv · 10.64898/2026.09.15.751278

Durability and diversity of human upper airway T cell memory

Ramirez, S. I.·Faraji, F.·Lopez, P. G.·Garin-Ortega, L.·Hern, N. A.·Eisenman, O.·Azhan, A.·Frazier, A.·Phillips, E. J.·Mallal, S.·Sette, A.·Dileepan, T.·Jenkins, M. K.·Crotty, S.

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Abstract

T cells are major contributors to protective immunity against pathogens and cancers. Immune memory is a central feature of protective adaptive immunity, and mucosal barrier tissues are major sites of pathogen invasion. Yet, fundamental gaps remain in our knowledge of human T cell immune memory durability in mucosal barrier sites. Here, we employed minimally invasive nasal swab sampling to directly detect, and longitudinally assess, human antigen-specific T cells in two upper airway tissue sites (~ 900 samples) and peripheral blood. Antigen-specific memory CD8 and CD4 T cells were detected in upper airway tissue of > 95% of individuals. Both memory CD8 and CD4 T cells were sustained in both mucosal epithelial and mucosal lymphoid tissue over the course of 18+ months, with monthly sampling, and no clear evidence of decline. Virus-specific upper airway CD8 and CD4 T cells were predominantly resident memory T cells (TRM) throughout the 18+ month period of observation. These findings can inform future T cell vaccines and therapeutics.

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Ramirez, S. I., Faraji, F., Lopez, P. G., Garin-Ortega, L., Hern, N. A., Eisenman, O., Azhan, A., Frazier, A., Phillips, E. J., Mallal, S., Sette, A., Dileepan, T., Jenkins, M. K., Crotty, S.. 2026-09-18. Durability and diversity of human upper airway T cell memory. https://doi.org/10.64898/2026.09.15.751278

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