• Alexander Gelbard, Celestine Wanjalla, Christopher T Wootten, Wonder P Drake, Anne S Lowery, David A Wheeler, Maria F Cardenas, Andrew G Sikora, Ravi R Pathak, Wyatt McDonnell, Simon Mallal, and Mark Pilkinton.
• Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.
• Laryngoscope. 2021 Mar 1; 131 (3): 610-617.

Objectives/HypothesisCharacterization of the localized adaptive immune response in the airway scar of patients with idiopathic subglottic stenosis (iSGS).Study DesignBasic Science.MethodsUtilizing 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.ResultsiSGS, 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 (TRM ) 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.ConclusionsThe 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, 131:610-617, 2021.© 2020 The American Laryngological, Rhinological and Otological Society, Inc.

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