Maggi E
Clinical Immunology Dept., University of Firenze, Italy.
Immunotechnology. 1998 Jan;3(4):233-44. doi: 10.1016/s1380-2933(97)10005-7.
Recent evidence has been accumulated to suggest that allergen-reactive type 2 helper T cells (Th2) play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, i.e. the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon (IFN-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta, and hormones, play a negative regulatory role on the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic individuals still remain obscure. Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been described. Moreover, cytokines and other gene products that dampen the production of IL-4, as well as the development and/or the function of Th2 cells, have been identified. These findings allow us to suggest that the up-regulation of genes controlling IL-4 expression and/or abnormalities of regulatory mechanisms of Th2 development and/or function may be responsible for Th2 responses against common environmental allergens in atopic people. The new insights in the pathophysiology of T cell responses in atopic diseases provide exciting opportunities for the development of novel immunotherapeutic strategies. They include the induction of nonresponsiveness in allergen-specific Th2 cells by allergen peptides or redirection of allergen-specific Th2 responses by Th1-inducing cytokines, altered peptide ligands, allergens incorporated into recombinant microorganisms or bound to appropriate adjuvants, and plasmid DNA vaccination. In severe atopic patients, the possibility of nonallergen-specific immunotherapeutic regimens designed to target Th2 cells or Th2-dependent effector molecules, such as specific IL-4 transcription factors, IL-4, IL-5 and IgE, may also be suggested.
最近积累的证据表明，过敏原反应性2型辅助性T细胞（Th2）在激活和/或募集产生IgE抗体的B细胞、肥大细胞和嗜酸性粒细胞（即参与过敏性炎症的细胞三联体）中起触发作用。在抗原呈递给Th细胞时，一种仍未知的细胞类型（T细胞亚群、肥大细胞/嗜碱性粒细胞？）产生的白细胞介素（IL）-4对Th2细胞的发育至关重要。其他细胞因子，如IL-1和IL-10，以及激素，如骨化三醇和孕酮，也起促进作用。相反，细胞因子如干扰素（IFN-α、IFN-γ、IL-12）和转化生长因子（TGF）-β，以及激素，对Th2细胞的发育起负调节作用。然而，特应性个体中Th2细胞被环境过敏原优先激活的潜在机制仍然不清楚。最近描述了一些在Th2细胞中选择性表达或选择性控制IL-4表达的基因产物。此外，已经鉴定出抑制IL-4产生以及Th2细胞发育和/或功能的细胞因子和其他基因产物。这些发现使我们认为，控制IL-4表达的基因上调和/或Th2发育和/或功能调节机制的异常可能是特应性个体针对常见环境过敏原的Th2反应的原因。特应性疾病中T细胞反应病理生理学的新见解为开发新的免疫治疗策略提供了令人兴奋的机会。这些策略包括通过过敏原肽诱导过敏原特异性Th2细胞无反应性，或通过Th1诱导细胞因子、改变的肽配体、掺入重组微生物或与适当佐剂结合的过敏原以及质粒DNA疫苗接种来重定向过敏原特异性Th2反应。在重度特应性患者中，也可能建议采用针对Th2细胞或Th2依赖性效应分子（如特异性IL-4转录因子、IL-4、IL-5和IgE）的非过敏原特异性免疫治疗方案。
