Allergen-Specific CD4+ T Cells in Human Asthma Have an Increased Capacity to Respond to Innate Type 2 Signals

Asthma is a common chronic inflammatory disease characterized by eosinophilic airway inflammation and airway hyperresponsiveness. We hypothesize that allergen-specific CD4+ T cells in the airway are critical drivers of allergic asthma. HLA-typed allergic asthmatic (AA, n=15) and allergic non-asthmatic (ANA, n=23) subjects were enrolled in a segmental allergen challenge (SAC) study. The leukocyte composition of the bronchoalveolar lavage (BAL) fluid was analyzed in cytospin preparations. BAL cytokine levels were measured using a Luminex assay. Allergen-specific CD4+ T cells in the BAL were analyzed by flow cytometry after staining with dust mite (Der p 1) or cat (Fel d 1)-specific class II tetramers and antibodies to innate type 2 cytokine receptors (IL-33R and IL-25R) and other Th2 surface markers (CRTH2 and CCR4). We found that both AA and ANA exhibited an increase in the number of allergen-specific CD4+ T cells in the BAL after SAC, but allergen-specific CD4+ T cells from AA exhibited increased IL-33R and CRTH2 expression compared with those from ANA. IL-33R expression on allergen-specific CD4+ T cells correlated with eosinophilia, IL-4, IL-5, IL-13, IL-9, and CCL26 in the BAL, all of which were detected at higher levels in AA compared to ANA post-challenge. These results suggest that allergen-specific CD4+ T cells in the airway of AA compared to ANA subjects have an increased capacity to respond to innate type 2 signals (IL-33 and PGD2), which correlates with airway eosinophilia and Th2-associated inflammation.