Immunological memory diversity in the human upper airway

• 成果类型: Article
• 署名作者: Ramirez, Sydney I.; Faraji, Farhoud; Hills, L. Benjamin; Lopez, Paul G.; Goodwin, Benjamin; Stacey, Hannah D.; Sutton, Henry J.; Hastie, Kathryn M.; Saphire, Erica Ollmann; Kim, Hyun Jik; Mashoof, Sara; Yan, Carol H.; DeConde, Adam S.; Levi, Gina; Crotty, Shane
• 署名单位: La Jolla Institute for Immunology; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Seoul National University (SNU)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6457
• DOI: 10.1038/s41586-024-07748-8
• 发表日期: 2024-08-15
• 关键词: t-cells; immunoglobulin; expression; toolkit; long

摘要

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. This study of immunological memory diversity in the human upper airway provides new understanding of immune memory at a major mucosal barrier tissue in humans.