Spazierer D, Skvara H, Dawid M, Fallahi N, Gruber K, Rose K, Lloyd P, Heuerding S, Stingl G, Jung T
Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Vienna Competence Center, 1090 Vienna, Austria.
Clin Exp Allergy. 2009 Jul;39(7):999-1008. doi: 10.1111/j.1365-2222.2008.03177.x. Epub 2009 Feb 19.
Allergen-specific T helper 2 (Th2) cells play an important role in the pathogenesis of atopic disorders. To date, no model system exists in humans that would allow the monitoring of a developing de novo Th2 immune response in vivo.
The aim of the experiment was to establish an immunization protocol inducing a de novo Th2 response in humans using Keyhole Limpet Hemocyanin (KLH) as neo-antigen.
The double-blind placebo-controlled, parallel-group study was conducted in two groups of subjects (16 healthy volunteers and 16 patients with allergic rhinitis). Subjects received three i.m. injections of 100 microg KLH adsorbed to aluminium hydroxide or matching placebo (alum alone) in intervals of 2 weeks. On day 43, KLH alone (10 microg) was given intra-dermally (i.d.) to all subjects to assess immediate and late-phase skin responses.
The immunization protocol was well tolerated, highly specific and efficient. Antigen-specific production of Th2-cytokines (mainly IL-5 and IL-13) by PBMCs suggested a Th2 pattern, as did the presence of KLH-specific IgG4 in sera. Intra-dermal KLH challenge induced an immediate-type of response predominantly in atopic subjects followed by a late-phase skin reaction. The latter was accompanied by the presence of IgE(+) cells, eosinophils and a strong up-regulation of IL-4 and IL-13 along with the absence of Th1 transcripts in biopsies taken from the site of antigen challenge. IL-17 and IL-22 transcripts were detected only in healthy subjects skin following KLH challenge, while IL-1beta and IL-33 expression did not differ between the healthy and the atopics.
The immunization protocol resulted in the elicitation of a local and peripheral Th2 immune response in both healthy and atopic individuals. This may permit the investigation and monitoring of novel immunomodulatory strategies aiming to interfere with Th2 responses in man. The relevance of lack of Th17 cells in atopic skin in this model remains to be determined.
变应原特异性辅助性T细胞2（Th2）在特应性疾病的发病机制中起重要作用。迄今为止，人类尚无能够在体内监测新发生的Th2免疫反应发展过程的模型系统。
本实验旨在建立一种免疫方案，以匙孔血蓝蛋白（KLH）作为新抗原在人体内诱导新发生的Th2反应。
本双盲、安慰剂对照、平行组研究在两组受试者（16名健康志愿者和16名变应性鼻炎患者）中进行。受试者每隔2周接受3次肌肉注射100μg吸附于氢氧化铝的KLH或匹配的安慰剂（仅明矾）。在第43天，对所有受试者进行皮内注射（i.d.）单独的KLH（10μg），以评估即刻和迟发性皮肤反应。
该免疫方案耐受性良好、高度特异且有效。外周血单核细胞（PBMC）产生的Th2细胞因子（主要是IL-5和IL-13）的抗原特异性表明为Th2模式，血清中存在KLH特异性IgG4也表明为Th2模式。皮内注射KLH激发主要在特应性受试者中诱导即刻型反应，随后是迟发性皮肤反应。后者伴有IgE（+）细胞、嗜酸性粒细胞的存在以及IL-4和IL-13的强烈上调，同时在抗原激发部位采集的活检组织中未检测到Th1转录本。仅在健康受试者皮肤经KLH激发后检测到IL-17和IL-22转录本，而健康受试者和特应性受试者之间IL-1β和IL-33的表达无差异。
该免疫方案在健康个体和特应性个体中均引发了局部和外周Th2免疫反应。这可能有助于研究和监测旨在干扰人类Th2反应的新型免疫调节策略。该模型中特应性皮肤中缺乏Th17细胞的相关性仍有待确定。
