Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma.

CD4 ⁺ T helper (T _H ) cells and regulatory T (T _reg ) cells that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive T _H and T _reg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive T _H cells and T _reg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and nonasthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive T _H and T _reg cells are highly heterogeneous and certain subsets are quantitatively and qualitatively different in individuals with HDM-reactive asthma. The number of interleukin-9 (IL-9)-expressing HDM-reactive T _H cells is greater in asthmatics with HDM allergy compared with nonasthmatics with HDM allergy, and this IL-9-expressing T _H subset displays enhanced pathogenic properties. More HDM-reactive T _H and T _reg cells expressing the interferon response signature (T _H IFNR and T _reg IFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (T _H IFNR and T _reg IFNR), expression of TNFSF10 was enriched; its product, tumor necrosis factor-related apoptosis-inducing ligand, dampens activation of T _H cells. These findings suggest that the T _H IFNR and T _reg IFNR subsets may dampen allergic responses, which may help explain why only some people develop T _H 2 responses to nearly ubiquitous allergens.
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