Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Allergy Clin Immunol. 2013 Jan;131(1):14-22. doi: 10.1016/j.jaci.2012.10.058.
Immune tolerance is defined as nonresponsiveness of the adaptive immune system to antigens. Immune mechanisms preventing inappropriate immune reactivity to innocuous antigens include deletion of reactive lymphocytes and generation of regulatory T (Treg) cells. The normal response to food antigens is the generation of antigen-specific Treg cells. In patients with food allergy, the dominant immune response is a T(H)2-skewed T-cell response and the generation of food-specific IgE antibodies from B cells. It is not known whether a failure of the Treg cell response is behind this inappropriate immune response, but interventions that boost the Treg cell response, such as mucosal immunotherapy, might lead to a restoration of immune tolerance to foods. Tolerance has been notoriously difficult to restore in animal disease models, but limited data from human trials suggest that tolerance (sustained nonresponsiveness) can be re-established in a subset of patients. Furthermore, studies on the natural history of food allergy indicate that spontaneous development of tolerance to foods over time is not uncommon. The current challenge is to understand the mechanisms responsible for restoration of natural or induced tolerance so that interventions can be developed to more successfully induce tolerance in the majority of patients with food allergy.
免疫耐受被定义为适应性免疫系统对抗原无反应。防止对无害抗原产生不当免疫反应的免疫机制包括反应性淋巴细胞的缺失和调节性 T（Treg）细胞的产生。正常情况下，机体对食物抗原的反应是产生抗原特异性的 Treg 细胞。在食物过敏患者中，主要的免疫反应是 T(H)2 偏向的 T 细胞反应和 B 细胞产生食物特异性 IgE 抗体。目前尚不清楚这种不当免疫反应背后是否是 Treg 细胞反应的失败，但增强 Treg 细胞反应的干预措施，如黏膜免疫疗法，可能会导致对食物的免疫耐受恢复。在动物疾病模型中，耐受的恢复一直是一个难题，但来自人类试验的有限数据表明，在一部分患者中可以重新建立耐受（持续无反应）。此外，对食物过敏自然史的研究表明，随着时间的推移，食物的自发耐受发展并不少见。目前的挑战是了解恢复自然或诱导耐受的机制，以便开发干预措施，更成功地诱导大多数食物过敏患者的耐受。
