Mechanisms of allergen-specific immunotherapy: Multiple suppressor factors at work in immune tolerance to allergens
Mechanisms of allergen-specific immunotherapy: Multiple suppressor factors at work in immune tolerance to allergens
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DOI：
10.1016/j.jaci.2013.12.1088
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发表时间：
2014-03-01
影响因子：
14.2
通讯作者：
Akdis, Cezmi A.
中科院分区：
文献类型：
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作者：
Akdis, Muebeccel;Akdis, Cezmi A.
过敏原特异性免疫疗法（AIT）作为IgE介导的过敏性疾病的脱敏疗法已经使用了100多年，并且代表了一种潜在的治疗方法。AIT的作用机制包括诱导肥大细胞和嗜碱性粒细胞的极早期脱敏;产生调节性T细胞和调节性B（布雷格）细胞应答;调节IgE和IgG（4）;减少粘膜过敏组织中嗜酸性粒细胞和肥大细胞的数量和活性;降低循环中嗜碱性粒细胞的活性。变应原特异性效应T细胞和效应B细胞向调节表型的偏移似乎是AIT和对变应原的正常免疫应答过程中的关键事件。最近，诱导型IL-10分泌型布雷格细胞也被证明通过抑制效应T细胞和选择性诱导IgG 4同种型抗体而有助于过敏原耐受。过敏原特异性调节性T细胞和布雷格细胞协调一般免疫调节活性，其可概括为抑制来自炎性树突细胞的细胞因子;抑制效应T（H）1、T（H）2和T（H）17细胞;抑制过敏原特异性IgE和诱导IgG（4）;以及抑制肥大细胞、嗜碱性粒细胞、嗜酸性粒细胞和效应T细胞向组织的迁移。详细了解AIT的机制不仅在设计过敏性疾病的预防和治疗中很重要，而且还可能在自身免疫性疾病、器官移植、慢性感染和癌症的治疗中找到应用。
Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a desensitizing therapy for IgE-mediated allergic diseases and represents a potentially curative way of treatment. The mechanisms of action of AIT include the induction of very early desensitization of mast cells and basophils; generation of regulatory T and regulatory B (Breg) cell responses; regulation of IgE and IgG(4); decreases in numbers and activity of eosinophils and mast cells in mucosal allergic tissues; and decreases in the activity of basophils in circulation. Skewing of allergen-specific effector T and effector B cells to a regulatory phenotype appears as a key event in the course of AIT and normal immune response to allergens. Recently, inducible IL-10-secreting Breg cells were also demonstrated to contribute to allergen tolerance through suppression of effector T cells and selective induction of IgG4 isotype antibodies. Allergen-specific regulatory T and Breg cells orchestrate a general immunoregulatory activity, which can be summarized as suppression of cytokines from inflammatory dendritic cells; suppression of effector T(H)1, T(H)2, and T(H)17 cells; suppression of allergen-specific IgE and induction of IgG(4); and suppression of migration of mast cells, basophils, eosinophils, and effector T cells to tissues. A detailed knowledge of the mechanisms of AIT is not only important in designing the prevention and treatment of allergic diseases but might also find applications in the treatment of autoimmune diseases, organ transplantation, chronic infection, and cancer.