Rolland J M, Douglass J, O'Hehir R E
Department of Pathology and Immunology, Monash University Medical School, Commercial Road, Prahran, Victoria 3181, Australia.
Expert Opin Investig Drugs. 2000 Mar;9(3):515-27. doi: 10.1517/13543784.9.3.515.
Allergic individuals respond to an environmental allergen encounter by producing T-cell cytokines, predominantly IL-4 and IL-5, which in turn drive the production of allergen-specific IgE antibodies and recruitment of an eosinophil-rich inflammatory infiltrate. Allergen-specific immunotherapy (SIT) involves the repeated injection of the allergen to specifically downregulate this predominantly Th2-type immune response. SIT is a clinically proven effective treatment for allergic diseases, including rhinoconjunctivitis and asthma. However, despite having been in clinical practice since early this century, its use remains empirical. Best practice protocols are based on clinical experience and include recommendations for selecting patients for treatment, SIT regimes and avoidance of adverse events. More rational and safer SIT regimes will result from new insights into the underlying immune mechanisms for allergic disease, in particular the critical role of helper T-cells in orchestrating this response. The development of recombinant techniques for producing purified allergens and allergen derivatives has led to a dramatic improvement in the ability to standardise allergen preparations and to develop novel vaccines for allergy treatment. Potential vaccines include short peptides based on dominant T-cell epitopes of allergens, allergen fragments and mutant allergens. All of these preparations are designed to target T-cells without binding IgE and inducing local and systemic side effects. Additional strategies under consideration include DNA vaccines and fusion protein constructs incorporating immunomodulatory elements such as bacterial cell proteins, cytokines and immunostimulatory sequences of DNA. Different forms of allergens are being evaluated for the more practical mucosal administration of allergy vaccines. The identification of recombinant allergens suitable for diagnostic use and the development of reliable laboratory assays, based on T-cell function to monitor clinical efficacy of SIT, are important practical outcomes from this research.
过敏个体在接触环境过敏原后会产生T细胞细胞因子，主要是白细胞介素-4和白细胞介素-5，这些细胞因子进而促使产生过敏原特异性IgE抗体，并募集富含嗜酸性粒细胞的炎性浸润物。过敏原特异性免疫疗法（SIT）包括反复注射过敏原，以特异性下调这种主要为Th2型的免疫反应。SIT是一种经临床验证对过敏性疾病（包括变应性鼻结膜炎和哮喘）有效的治疗方法。然而，尽管自本世纪初以来就已应用于临床实践，但其使用仍基于经验。最佳实践方案基于临床经验，包括选择治疗患者的建议、SIT方案以及避免不良事件。对过敏性疾病潜在免疫机制的新见解，特别是辅助性T细胞在协调这种反应中的关键作用，将带来更合理、更安全的SIT方案。生产纯化过敏原和过敏原衍生物的重组技术的发展，极大地提高了标准化过敏原制剂的能力，并推动了用于过敏治疗的新型疫苗的研发。潜在的疫苗包括基于过敏原主要T细胞表位的短肽、过敏原片段和突变过敏原。所有这些制剂的设计目的都是靶向T细胞，而不结合IgE并诱导局部和全身副作用。正在考虑的其他策略包括DNA疫苗和融合蛋白构建体，其中包含免疫调节元件，如细菌细胞蛋白、细胞因子和DNA的免疫刺激序列。正在评估不同形式的过敏原，以便更实际地进行过敏疫苗的黏膜给药。鉴定适合诊断用途的重组过敏原以及开发基于T细胞功能来监测SIT临床疗效的可靠实验室检测方法，是这项研究的重要实际成果。
