Romagnani Sergio
Section of Clinical Immunology, Allergy, and Respiratory Diseases, Department of Internal Medicine, University of Florence, Italy.
J Allergy Clin Immunol. 2004 Mar;113(3):395-400. doi: 10.1016/j.jaci.2003.11.025. Epub 2004 Feb 1.
TH2 cell-mediated immune responses against "innocuous" antigens play a triggering role in atopic allergy. Several epidemiologic studies have clearly shown that the reduced microbial exposure of children caused by the westernized lifestyle is responsible for the increased prevalence of allergy that has occurred in the last decades in developed countries ("hygiene hypothesis"). The immunologic changes caused by the reduced exposure to pathogenic and nonpathogenic microbes during childhood are still controversial. The initial interpretation has been a lack of shift of allergen-specific responses from the TH2 to the TH1 phenotype. This is because of reduced production of IL-12 and IFNs by cells of the natural immunity stimulated by bacterial products through their Toll-like receptors (missing immune deviation). Another interpretation emphasizes the importance of reduced activity of T-regulatory cells (reduced immune suppression). However, although there are impressive amounts of data in favor of the missing immune deviation, experimental evidence supporting the role of reduced immune suppression in explaining the increased prevalence of allergy is currently weak or even contradictory. The solution to this question is very important not only from a theoretic point of view but also because of its therapeutic implications.
针对“无害”抗原的TH2细胞介导的免疫反应在特应性过敏中起触发作用。多项流行病学研究清楚地表明，西方化生活方式导致儿童接触微生物减少，这是过去几十年来发达国家过敏患病率增加的原因（“卫生假说”）。儿童期接触致病和非致病微生物减少所引起的免疫变化仍存在争议。最初的解释是过敏原特异性反应缺乏从TH2表型向TH1表型的转变。这是因为细菌产物通过其Toll样受体刺激天然免疫细胞产生的IL-12和IFN减少（免疫偏移缺失）。另一种解释强调T调节细胞活性降低（免疫抑制减弱）的重要性。然而，尽管有大量令人印象深刻的数据支持免疫偏移缺失，但目前支持免疫抑制减弱在解释过敏患病率增加中作用的实验证据薄弱甚至相互矛盾。这个问题的解决不仅从理论角度非常重要，而且因其治疗意义也很重要。
