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 diseases1-4. 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.
摘要：
上呼吸道是重要的感染部位,但是人类上呼吸道的免疫记忆知之甚少，对COVID-19和许多其他人类疾病有影响1-4。在这里，我们证明了鼻和鼻咽拭子可以用来获得对这些具有挑战性的问题的见解，定义不同的免疫细胞群，包括抗原特异性记忆B细胞和T细胞,在上呼吸道的两个相邻解剖部位。在每月接受拭子超过1年的健康成年人中，上呼吸道免疫细胞群随着时间的推移似乎是稳定的。定义了突出的组织驻留记忆T（TRM）细胞和B（BRM）细胞群。出乎意料的是,在许多鼻咽拭子中发现了生发中心细胞。在SARS-CoV-2突破性感染的受试者中，局部病毒特异性BRM细胞，确定了浆细胞和生发中心B细胞，有证据表明，与血液相比，上呼吸道隔室中IgA记忆B细胞的局部引发和富集。鉴定了具有长寿转录谱的局部浆细胞群。鉴定了局部病毒特异性记忆CD4+TRM细胞和CD8+TRM细胞，具有多种额外的病毒特异性T细胞。观察到年龄依赖性上呼吸道免疫变化。这些发现为人类主要粘膜屏障组织的免疫记忆提供了新的理解。
