Data_Sheet_1_Th2-TRMs Maintain Life-Long Allergic Memory in Experimental Asthma in Mice.pdf

Allergic asthma is a chronic inflammatory remitting-relapsing disease affecting the airways. Long-lived allergen-specific memory CD4+ T helper 2 (Th2) cells in mice persist in lungs for more than 2 years after the induction of experimental allergic asthma (EAA). To further understand lung Th2 memory cells, we tracked CD4+ T cells in spleen and lungs from healthy mice, through the initiation of acute EAA, recovery (remission), and allergen-induced disease relapse. We identified a lung CD3+CD4+ cell subset that expresses CD44hiCD62L−CD69+ST2+, produces Th2 cytokines, and mediates allergen-induced disease relapse despite treatment with FTY720 and anti-CD4 antibody. These cells reside in the lung tissue for the lifetime of mice (>665 days) and represent long-lived pathogenic Th2 tissue resident memory cells (TRMs) that maintain “allergic memory” in lung. We speculate that these data implicate that human Th2-TRMs sentinels in lungs of patients are poised to rapidly respond to inhaled allergen and induce asthma attacks and that therapeutic approaches targeting these cells may provide relief to patients with allergic asthma.

过敏性哮喘是一种影响呼吸道的慢性炎症性疾病，具有反复发作的特性。在实验性过敏性哮喘（EAA）诱导后，小鼠体内的长期存活过敏原特异性记忆CD4+ Th2辅助性T细胞在肺部可维持超过两年。为进一步揭示肺部Th2记忆细胞的作用，本研究追踪了健康小鼠脾脏和肺部中的CD4+ T细胞，从急性EAA的起始、恢复（缓解）以及过敏原诱导的疾病复发阶段。我们鉴定出一种肺部CD3+CD4+细胞亚群，该亚群表达CD44hiCD62L−CD69+ST2+，产生Th2细胞因子，并在接受FTY720和抗CD4抗体治疗后仍介导过敏原诱导的疾病复发。这些细胞在小鼠生命周期内（>665天）驻留在肺部组织，代表了一种长期存在的致病性Th2组织驻留记忆细胞（TRMs），它们在肺部维持“过敏记忆”。我们推测，这些数据表明，患者肺部中的Th2-TRMs哨兵细胞能够迅速对吸入的过敏原做出反应，并引发哮喘发作，针对这些细胞的治疗方法可能为过敏性哮喘患者带来缓解。