Allergen recognition by specific effector Th2 cells enables IL-2-dependent activation of regulatory T-cell responses in humans.
Allergen recognition by specific effector Th2 cells enables IL-2-dependent activation of regulatory T-cell responses in humans.
复制标题
特定效应 Th2 细胞对过敏原的识别使得人类调节性 T 细胞反应能够依赖 IL-2 激活。
DOI：
10.1111/all.15512
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发表时间：
2023
期刊：
影响因子：
12.4
通讯作者：
Berin,MCecilia
中科院分区：
文献类型：
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作者：
Lozano-Ojalvo,Daniel;Tyler,ScottR;Aranda,CarlosJ;Wang,Julie;Sicherer,Scott;Sampson,HughA;Wood,RobertA;Burks,AWesley;Jones,StacieM;Leung,DonaldYM;deLafaille,MariaCurotto;Berin,MCecilia
2型过敏原特异性T细胞对于食物过敏的诱导和维持至关重要，而这些过敏原特异性的Tregs被认为参与了它们的解决。然而，目前还没有令人信服的证据表明，过敏原特异性Treg反应是否导致了人类口腔耐受的产生。我们观察到，以口服免疫疗法的形式持续暴露于食物过敏原导致Tregs的频率增加，只有在持续临床耐受的个体中。我们试图通过研究CD4+T细胞随时间在体内和体外的功能激活来确定它们对食物过敏原反应的调节成分。与克隆富集的致病效应Th2细胞相比，表达CD137或CD25/OX40的两个Tregs亚群被鉴定出具有延迟激活动力学。Treg的激活依赖于来自效应T细胞的IL - 2。在体内暴露于花生的形式的口服食物挑战过敏受试者诱导延迟和持续激活Tregs后，启动过敏原特异性Th2反应。本研究的新发现是，Th2效应细胞释放IL - 2可诱导Treg激活的持续波，这意味着IL - 2的治疗性管理可以改善当前的OIT方法。
Type 2 allergen‐specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen‐specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance. We sought to identify regulatory components of the CD4+T‐cell response to food allergens by studying their functional activation over time in vitro and in vivo. Two subsets of Tregs expressing CD137 or CD25/OX40 were identified with a delayed kinetics of activation compared with clonally enriched pathogenic effector Th2 cells. Treg activation was dependent on IL‐2 derived from effector T cells. In vivo exposure to peanut in the form of an oral food challenge of allergic subjects induced a delayed and persistent activation of Tregs after initiation of the allergen‐specific Th2 response. The novel finding of our work is that a sustained wave of Treg activation is induced by the release of IL‐2 from Th2 effector cells, with the implication that therapeutic administration of IL‐2 could improve current OIT approaches.