%0 Journal Article
%T Immunological memory diversity in the human upper airway.
%A Ramirez SI
%A Faraji F
%A Hills LB
%A Lopez PG
%A Goodwin B
%A Stacey HD
%A Sutton HJ
%A Hastie KM
%A Saphire EO
%A Kim HJ
%A Mashoof S
%A Yan CH
%A DeConde AS
%A Levi G
%A Crotty S
%J Nature
%V 632
%N 8025
%D 2024 Aug 31
%M 39085605
%F 69.504
%R 10.1038/s41586-024-07748-8
%X The upper airway is an important site of infection, but immune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problems, and define distinct immune cell populations, including antigen-specific memory B cells and T cells, in two adjacent anatomical sites in the upper airway. Upper airway immune cell populations seemed stable over time in healthy adults undergoing monthly swabs for more than 1 year, and prominent tissue resident memory T (TRM) cell and B (BRM) cell populations were defined. Unexpectedly, germinal centre cells were identified consistently in many nasopharyngeal swabs. In subjects with SARS-CoV-2 breakthrough infections, local virus-specific BRM cells, plasma cells and germinal centre B cells were identified, with evidence of local priming and an enrichment of IgA+ memory B cells in upper airway compartments compared with blood. Local plasma cell populations were identified with transcriptional profiles of longevity. Local virus-specific memory CD4+ TRM cells and CD8+ TRM cells were identified, with diverse additional virus-specific T cells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.