Distinct phenotypes and repertoires of bronchoalveolar and airway mucosal T cells in health and allergic asthma

T cells play a central role in host protection against respiratory pathogens, but a maladaptive T cell response can lead to pulmonary diseases. Defining the biology of protective versus pathogenic T cell responses in the lungs of humans will be critical to nominate novel approaches to improve respiratory health. Previous studies have examined T cells from the lungs captured via bronchoalveolar lavage (BAL), endobronchial brushings, or biopsies. However, whether these different approaches are capturing distinct T cell phenotypes and/or clonotypes remains unclear. We aimed to evaluate and compare the transcriptional signatures of T cells isolated via BAL versus endobronchial brushings in healthy controls (HCs) and allergic asthmatics (AAs). The most significant difference in T cell subsets abundance between AAs and HCs was the enrichment of CD4 T helper type 2 (Th2) cells when comparing endobronchial brush samples (OR=26.2, P=0.002), but not when examining BAL (OR=1.7, P=0.46), indicating differences in the T cell subsets captured from the BAL versus airway mucosa specimen processing. TCR repertoire analysis revealed that brush T cells contained dramatically expanded TCR clones. Expanded T cell clones from the brush expressed high levels of resident-memory markers, suggesting the airway mucosa is enriched for TRM cells with unique TCR specificity.