Verhagen Johan, Blaser Kurt, Akdis Cezmi A, Akdis Mübeccel
Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland.
Immunol Allergy Clin North Am. 2006 May;26(2):207-31, vi. doi: 10.1016/j.iac.2006.02.008.
Activation-induced cell death, anergy, or immune response modulation by regulatory T cells (Treg cells) are essential mechanisms of peripheral T-cell tolerance. Genetic predisposition and environmental instructions tune thresholds for the activation of T cells, other inflammatory cells, and resident tissue cells in allergic diseases. Skewing allergen-specific effector T cells to a Treg-cell phenotype seems to be crucial in maintaining a healthy immune response to allergens and successful allergen-specific immunotherapy. The Treg-cell response is characterized by an abolished allergen-specific T-cell proliferation and the suppressed secretion of T-helper 1- and T-helper 2-type cytokines. Suppressed proliferative and cytokine responses against allergens are induced by multiple suppressor factors, including cytokines such as interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), and cell surface molecules such as cytotoxic T-lymphocyte antigen-4, programmed death-1, and histamine receptor 2. The increased levels of IL-10 and TGF-beta produced by Treg cells potently suppress IgE production while simultaneously increasing the production of noninflammatory isotypes IgG4 and IgA, respectively. In addition, Treg cells directly or indirectly suppress the activity of effector cells of allergic inflammation, such as mast cells, basophils, and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms on T cells, regulation of antibody isotypes, and suppression of effector cells. The application of current knowledge of Treg cells and related mechanisms of peripheral tolerance may soon lead to more rational and safer approaches to the prevention and cure of allergic disease.
活化诱导的细胞死亡、无能或调节性T细胞（Treg细胞）介导的免疫反应调节是外周T细胞耐受的重要机制。遗传易感性和环境因素调节过敏性疾病中T细胞、其他炎症细胞和组织驻留细胞的激活阈值。将过敏原特异性效应T细胞偏向Treg细胞表型似乎对于维持对过敏原的健康免疫反应和成功的过敏原特异性免疫治疗至关重要。Treg细胞反应的特征是过敏原特异性T细胞增殖被消除以及辅助性T细胞1型和辅助性T细胞2型细胞因子的分泌受到抑制。针对过敏原的增殖和细胞因子反应受到多种抑制因子的诱导，包括白细胞介素-10（IL-10）和转化生长因子β（TGF-β）等细胞因子，以及细胞毒性T淋巴细胞抗原-4、程序性死亡-1和组胺受体2等细胞表面分子。Treg细胞产生的IL-10和TGF-β水平升高，可有效抑制IgE的产生，同时分别增加非炎症性同种型IgG4和IgA的产生。此外，Treg细胞直接或间接抑制过敏性炎症效应细胞的活性，如肥大细胞、嗜碱性粒细胞和嗜酸性粒细胞。总之，对外周过敏原的耐受由T细胞上的多种主动抑制机制、抗体同种型的调节以及效应细胞的抑制来控制。应用目前关于Treg细胞和外周耐受相关机制的知识可能很快会带来更合理、更安全的过敏性疾病预防和治疗方法。
