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The Proximal Airway Is a Reservoir for Adaptive Immunologic Memory in Idiopathic Subglottic Stenosis
Author(s) -
Gelbard Alexander,
Wanjalla Celestine,
Wootten Christopher T.,
Drake Wonder P.,
Lowery Anne S.,
Wheeler David A.,
Cardenas Maria F.,
Sikora Andrew G.,
Pathak Ravi R.,
McDonnell Wyatt,
Mallal Simon,
Pilkinton Mark
Publication year - 2021
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.28840
Subject(s) - subglottic stenosis , airway , medicine , immune system , cd8 , stenosis , t cell receptor , immunohistochemistry , t cell , pathology , immunology , surgery
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 , 131:610–617, 2021