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_HIFNR and T_regIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (T_HIFNR and T_regIFNR), 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_HIFNR and T_regIFNR subsets may dampen allergic responses, which may help explain why only some people develop T_H2 responses to nearly ubiquitous allergens.

对常见过敏原有反应的CD4 ⁺ T辅助细胞（T _H）和调节性T（T _reg）细胞在驱动和缓解哮喘患者的气道炎症中起着重要作用。直到最近，对过敏原反应性T _H和T _reg细胞进行直接，无偏见的分子分析还是不可能的。为了更好地了解这些T细胞亚群在过敏和哮喘中的多样性，我们分析了约50,000个屋尘螨（HDM）过敏原反应性T _H细胞和T _reg的单细胞转录组来自具有HDM过敏的哮喘患者和三个对照组的细胞：没有HDM过敏的哮喘患者和有和没有HDM过敏的非哮喘患者。我们的分析表明，HDM过敏性哮喘患者中，HDM过敏原反应性T _H和T _reg细胞异质性很高，某些亚群在数量和质量上均存在差异。与非哮喘患者相比，对HDM过敏的哮喘患者中表达白介素9（IL-9）的HDM反应性T _H细胞数量更多，并且这种IL-9表达的T _H亚型显示出增强的致病特性。更多的HDM反应性T _H和T _reg细胞表达干扰素反应信号（T _H与具有HDM过敏的哮喘患者相比，没有HDM过敏的哮喘患者中存在IFNR和T _reg IFNR。在从这些子集（T细胞_ħ IFNτ之和T _REG IFNτ之），的表达TNFSF10富集; 其产物，肿瘤坏死因子相关的凋亡诱导配体，抑制T _H细胞的活化。这些发现表明，T _H IFNR和T _reg IFNR亚型可能会抑制过敏反应，这可能有助于解释为什么只有部分人对几乎无处不在的过敏原产生T _H 2反应。