美国拉霍亚免疫学研究所Shane Crotty团队在Nature上发表了题为Immunological memory diversity in the human upper airway的研究论文，研究表明鼻腔和鼻咽拭子可以用来研究上呼吸道的免疫记忆，包括抗原特异性B细胞和T细胞的存在和持久性。本研究提供了利用鼻拭子和鼻咽拭子研究复杂免疫学问题的思路和方法，定义了上呼吸道两个相邻部位的不同免疫细胞群体，包括抗原特异性记忆B细胞和T细胞。在一年多的每月采样中，健康成人的上呼吸道免疫细胞群体表现出时间上的稳定性和显著的驻留特性。在新冠突破性感染个体中，研究发现局部呼吸道中存在驻留B细胞、浆细胞和生发中心B细胞，且IgA亚型记忆B细胞在上呼吸道区域中富集，显示局部初始免疫反应。局部浆细胞表现出与长寿命相关的转录特征，同时发现了局部的病毒特异性呼吸道驻留记忆CD4+和CD8+ T细胞，以及多样化的其他病毒特异性T细胞。这些发现为理解人类主要黏膜屏障组织中的免疫记忆提供了新的视角。
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 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.