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

Laryngoscope. 2021 Mar;131(3):610-617. doi: 10.1002/lary.28840. Epub 2020 Jun 30.


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 (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.

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.

Keywords: T cell receptor; TCR sequencing; clonotype; iSGS; resident memory; subglottis.

MeSH terms

  • Adult
  • Aged
  • Airway Obstruction / immunology*
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • CD8 Antigens / immunology
  • Cicatrix / immunology*
  • Constriction, Pathologic
  • Female
  • Glottis / immunology
  • Glottis / pathology
  • Humans
  • Immunohistochemistry
  • Immunologic Memory / immunology*
  • Integrin alpha Chains / immunology
  • Laryngostenosis / immunology*
  • Lectins, C-Type / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • CD8 Antigens
  • Integrin alpha Chains
  • Lectins, C-Type
  • alpha E integrins