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The Proximal Airway Is a Reservoir for Adaptive Immunologic Memory in Idiopathic Subglottic Stenosis

机译:近端气道是特发性脱墨狭窄中适应性免疫记忆的储层

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Objectives/Hypothesis Characterization of the localized adaptive immune response in the airway scar of patients with idiopathic subglottic stenosis (iSGS). Study Design Basic Science. Methods Utilizing 36 patients with subglottic stenosis (25 idiopathic subglottic stenosis [iSGS], 10 iatrogenic post-intubation stenosis [iLTS], and one granulomatosis with polyangiitis [GPA]) we applied immunohistochemical and immunologic techniques coupled with RNA sequencing. Results iSGS, iLTS, and GPA demonstrate a significant immune infiltrate in the subglottic scar consisting of adaptive cell subsets (T cells along with dendritic cells). Interrogation of T cell subtypes showed significantly more CD69(+)CD103(+)CD8(+)tissue resident memory T cells (T-RM) in the iSGS airway scar than iLTS specimens (iSGS vs. iLTS; 50% vs. 28%,P= .0065). Additionally, subglottic CD8(+)clones possessed T-cell receptor (TCR) sequences with known antigen specificity for viral and intracellular pathogens. Conclusions The human subglottis is significantly enriched for CD8(+)tissue resident memory T cells in iSGS, which possess TCR sequences proven to recognize viral and intracellular pathogens. These results inform our understanding of iSGS, provide a direction for future discovery, and demonstrate immunologic function in the human proximal airway.Laryngoscope, 2020
机译:目的/假设特发性声门下狭窄(iSGS)患者气道瘢痕局部适应性免疫反应的特征。学习设计基础科学。方法利用36例声门下狭窄患者(25例特发性声门下狭窄[iSGS],10例医源性插管后狭窄[iLTS],1例伴多血管炎的肉芽肿[GPA]),应用免疫组织化学和免疫学技术结合RNA测序。结果iSGS、ILT和GPA在由适应性细胞亚群(T细胞和树突状细胞)组成的声门下瘢痕中显示出明显的免疫浸润。对T细胞亚型的询问显示,iSGS气道瘢痕中的CD69(+)CD103(+)CD8(+)组织驻留记忆T细胞(T-RM)明显多于iLTS标本(iSGS与iLTS;50%与28%,P=0.0065)。此外,声门下CD8(+)克隆具有T细胞受体(TCR)序列,该序列对病毒和细胞内病原体具有已知的抗原特异性。结论ISG中的CD8(+)组织驻留记忆T细胞在人声门下显著富集,其TCR序列已被证明可识别病毒和细胞内病原体。这些结果为我们理解iSGS提供了信息,为未来的发现提供了方向,并证明了人类近端气道的免疫功能。喉镜,2020年

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