López-Fandiño Rosina
Instituto de Investigación en Ciencias de la Alimentación (CIAL, CSIC-UAM), Madrid, Spain.
Front Immunol. 2025 Jun 12;16:1595696. doi: 10.3389/fimmu.2025.1595696. eCollection 2025.
Allergen-specific CD4 T cells play a pivotal role in the pathophysiology of food allergy and in the induction of tolerance during desensitization. However, their study remains challenging due to the considerable heterogeneity in the frequency and phenotype of food allergy-specific Th2 cells in allergic individuals, together with an extremely low abundance of T cells specific to a given allergen. Furthermore, a major limitation of human studies is their reliance on peripheral blood sampling, whereas higher frequencies of allergen-specific cells may reside in intestinal tissues directly implicated in the allergic response. Among the most targeted approaches to quantify and characterize these cells stand MHC class II tetramers and activation-based detection methods. These techniques have identified pathogenic Th2 cell subpopulations in allergic individuals, that are absent in non-allergic subjects and differentiate patients with diverse degrees of clinical reactivity. These cells, crucial in driving immune responses and mediating immunological memory, exhibit distinct phenotypic and functional properties compared to conventional Th2 cells. However, there is no conclusive evidence supporting a definitive role for allergen-specific regulatory T (Treg) cells in food allergy, natural tolerance, or desensitization following immunotherapy. Moreover, pathogenic Th2 and Treg cells may differ in their allergen specificity, potentially due to priming by distinct sets of food-derived antigens. A deeper understanding of the characteristics and roles of specific pathogenic Th2 and Treg cell populations in food allergy could pave the way for novel preventive and therapeutic strategies for this disease.
变应原特异性CD4 T细胞在食物过敏的病理生理学以及脱敏过程中的耐受诱导中起关键作用。然而,由于过敏个体中食物过敏特异性Th2细胞的频率和表型存在相当大的异质性,以及特定变应原特异性T细胞的丰度极低,对它们的研究仍然具有挑战性。此外,人体研究的一个主要局限性在于其依赖外周血采样,而更高频率的变应原特异性细胞可能存在于直接参与过敏反应的肠道组织中。在量化和表征这些细胞的最具针对性的方法中,有MHC II类四聚体和基于激活的检测方法。这些技术已经在过敏个体中鉴定出致病性Th2细胞亚群,这些亚群在非过敏个体中不存在,并且可以区分具有不同临床反应程度的患者。这些细胞在驱动免疫反应和介导免疫记忆方面至关重要,与传统Th2细胞相比,表现出独特的表型和功能特性。然而,没有确凿的证据支持变应原特异性调节性T(Treg)细胞在食物过敏、天然耐受或免疫治疗后的脱敏中起明确作用。此外,致病性Th2细胞和Treg细胞的变应原特异性可能不同,这可能是由于不同的食物衍生抗原引发所致。更深入地了解食物过敏中特定致病性Th2细胞和Treg细胞群体的特征和作用,可能为这种疾病的新型预防和治疗策略铺平道路。
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