美国拉霍亚免疫学研究所Shane Crotty小组揭示人类上呼吸道的免疫记忆多样性。2024年7月31日，《自然》杂志在线发表了这项成果。
据研究人员介绍，上呼吸道是感染的重要部位，但人类上呼吸道的免疫记忆尚不完全了解，这对COVID-19及许多其他人类疾病有重要影响。
研究人员展示了鼻腔和鼻咽拭子可以用于深入研究这些复杂问题，并在上呼吸道两个相邻解剖部位定义了不同的免疫细胞群体，包括抗原特异性记忆B细胞和T细胞。在健康成人中，经过超过1年的每月拭子采样，上呼吸道免疫细胞群体似乎稳定，并定义了显著的组织驻留记忆T细胞（TRM）和B细胞（BRM）群体。出乎意料地，许多鼻咽拭子中一致检测到了生发中心细胞。
在SARS-CoV-2突破性感染的受试者中，研究人员检测到了局部病毒特异性BRM细胞、浆细胞和生发中心B细胞，并有局部启动的证据，以及在上呼吸道区室中IgA+记忆B细胞的富集。局部浆细胞群体的转录谱表现出长期存在的特征。局部病毒特异性CD4+ TRM细胞和CD8+ TRM细胞被识别，同时存在多样化的其他病毒特异性T细胞。观察到与年龄相关的上呼吸道免疫学变化。这些发现提供了对人类主要黏膜屏障组织中免疫记忆的新理解。
附：英文原文
Title: Immunological memory diversity in the human upper airway
Author: 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
Issue&Volume: 2024-07-31
Abstract: 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 diseases1,2,3,4. 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 Tcells, 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 1year, 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 Bcells were identified, with evidence of local priming and an enrichment of IgA+ memory Bcells 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 Tcells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.
DOI: 10.1038/s41586-024-07748-8
Source: https://www.nature.com/articles/s41586-024-07748-8