Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs
Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs
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DOI：
10.1016/j.jaci.2012.02.037
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发表时间：
2012-06-01
影响因子：
14.2
通讯作者：
Ehlers, Marc
中科院分区：
文献类型：
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作者：
Oefner, Carolin M.;Winkler, Andre;Ehlers, Marc
背景：在炎症条件下，T细胞依赖（TD）蛋白抗原诱导促炎T细胞和b细胞反应。相反，在没有共刺激的情况下，由TD抗原诱导耐受性会触发调节性T细胞的发育。在这两种情况下都会产生IgG抗体，但它们是否具有不同的免疫调节功能尚不清楚。目的：近年来研究表明，IgG分子的促炎或抗炎作用是由不同的Fc - n链糖基化模式决定的。我们试图检测在TD耐受诱导下形成的IgG分子的Fc糖基化和抗炎质量。方法：分别给小鼠注射鸡卵白蛋白（OVA），观察OVA反应性IgG Fc糖基化情况。在树突状细胞培养和变应性气道疾病的体内模型中，进一步研究了差异糖基化抗ova igg的抗炎功能。此外，我们分析了患者在成功的过敏原特异性免疫治疗后桦树花粉反应性血清igg的Fc糖基化模式。结果：炎症条件下用TD抗原刺激可诱导表达低水平α 2,6-唾液基转移酶的浆细胞并产生去盐化的igg。相比之下，耐受诱导的浆细胞不会下调α 2,6-唾液基转移酶的表达，并分泌免疫抑制唾液基化的igg，这些igg足以阻止抗原特异性T细胞和b细胞反应、树突状细胞成熟和过敏性气道炎症。重要的是，在过敏患者中成功的特异性免疫治疗也诱导了唾液化的过敏原特异性igg。结论：我们的数据显示了一种新的抗原特异性免疫调节机制，由抗炎唾液化的igg介导，该机制是在TD耐受诱导下形成的。这些发现可能有助于开发新的抗原特异性治疗过敏和自身免疫。[J] .中华过敏症杂志，2012;29(1):1 - 4。
Background: Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T-and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. Objective: It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction.Methods: We administered chicken ovalbumin (OVA) with or without costimulus to mice and analyzed OVA-reactive IgG Fc glycosylation. The anti-inflammatory function of differentially glycosylated anti-OVA IgGs was further investigated in studies with dendritic cell cultures and in an in vivo model of allergic airway disease. Additionally, we analyzed the Fc glycosylation pattern of birch pollen-reactive serum IgGs after successful allergen-specific immunotherapy in patients.Results: Stimulation with TD antigens under inflammatory conditions induces plasma cells expressing low levels of alpha 2,6-sialyltransferase and producing desialylated IgGs. In contrast, plasma cells induced on tolerance induction did not downregulate alpha 2,6-sialyltransferase expression and secreted immunosuppressive sialylated IgGs that were sufficient to block antigen-specific T- and B-cell responses, dendritic cell maturation, and allergic airway inflammation. Importantly, successful specific immunotherapy in allergic patients also induced sialylated allergen-specific IgGs.Conclusions: Our data show a novel antigen-specific immunoregulatory mechanism mediated by anti-inflammatory sialylated IgGs that are formed on TD tolerance induction. These findings might help to develop novel antigen-specific therapies for the treatment of allergy and autoimmunity. (J Allergy Clin Immunol 2012;129:1647-55.)