Low-Dose IL-2 Induces Regulatory T Cell-Mediated Control of Experimental Food Allergy
Low-Dose IL-2 Induces Regulatory T Cell-Mediated Control of Experimental Food Allergy
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DOI：
10.4049/jimmunol.1501271
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发表时间：
2016-07-01
影响因子：
4.4
通讯作者：
Bellier, Bertrand
中科院分区：
文献类型：
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作者：
Bonnet, Benjamin;Vigneron, James;Bellier, Bertrand
调节性T细胞（Tcells）是维持免疫自身耐受的关键，并且还调节对外源性Ag（包括过敏原）的免疫应答。据报道，在过敏性患者中，Treg数量和功能均降低，这提供了新的治疗前景。我们以前证明，TCLB可以选择性地扩大和激活低剂量的IL-2（1d-IL-2）诱导免疫调节，而没有免疫抑制，并建立了自身免疫性疾病的保护作用。在这项研究中，我们评估了Id-IL-2在食物过敏实验模型中控制过敏的能力。Ld-IL-2诱导Treg扩增和活化，其在具有OVA和花生的两种小鼠模型中引起针对食物过敏的临床表现的保护。这种临床效果在Treg耗尽的小鼠中丧失，证明了Tlag在Id-IL-2功效中的主要贡献。机制研究进一步表明，对过敏的保护可以通过Treg依赖性的Th 1/Th 2平衡的局部修饰和肥大细胞募集和活化的抑制来解释。在7个月的时间内观察ld-IL-2的预防和治疗效果，突出其长期疗效。本研究表明，Id-IL-2是有效的预防和治疗过敏性免疫反应，因此代表了一个有前途的治疗策略，用于管理过敏性疾病。
Regulatory T cells (Tregs) are pivotal for maintenance of immune self-tolerance and also regulate immune responses to exogenous Ags, including allergens. Both decreased Treg number and function have been reported in allergic patients, offering new therapeutic perspectives. We previously demonstrated that Tregs can be selectively expanded and activated by low doses of IL-2 (1d-IL-2) inducing immunoregulation without immunosuppression and established its protective effect in autoimmune diseases. In this study, we evaluated the ability of Id-IL-2 to control allergy in an experimental model of food allergy. Ld-IL-2 induced Treg expansion and activation that elicited protection against clinical manifestations of food allergy in two mouse models with OVA and peanut. This clinical effect was lost in Treg-depleted mice, demonstrating the major contribution of Tregs in Id-IL-2 efficacy. Mechanistic studies further indicated that protection from allergy could be explained by a Treg-dependent local modification of the Th1/Th2 balance and an inhibition of mast cell recruitment and activation. Preventive and therapeutic effects of ld-IL-2 were observed over a 7-mo-period, highlighting its long-term efficacy. This study demonstrated that Id-IL-2 is efficient to prevent and to treat allergic immune responses, and thus represents a promising therapeutic strategy for managing allergic diseases.