Skrindo I, Ballke C, Gran E, Johansen F-E, Baekkevold E S, Jahnsen F L
Department of Pathology and Centre for Immune Regulation, Oslo University Hospital and University of Oslo, Oslo, Norway.
Department of Otorhinolaryngology, Akershus University Hospital, Lørenskog, Norway.
Clin Exp Allergy. 2015 Aug;45(8):1296-304. doi: 10.1111/cea.12543.
Seasonal allergic rhinitis is a chronic inflammation in the nasal mucosa triggered by inhaled aeroallergens. The inflammatory reaction is controlled by allergen-specific T cells, but where and how these T cells become activated is not fully understood.
We wanted to determine whether allergen-specific T-helper (Th) 2 cells are residing in the nasal mucosa under steady-state conditions outside of the pollen season and, if so, whether these cells are activated locally in response to allergen challenge.
Mucosal biopsies from the lower turbinate were obtained out of season from patients with either birch- or grass-pollen-allergic rhinitis and from healthy controls. Cultured explant samples were challenged with relevant pollen extract or with a mix of overlapping 20-mer peptides derived from the sequence of the major birch allergen, Betula verrucosa (Bet v) 1. After 24 h, culture medium was harvested for multiplex cytokine and tryptase analysis.
Significant amounts of interleukin (IL)-5 were secreted from resident cells in response to ex vivo allergen challenge in the allergic group only. No increase was observed for the other cytokines measured. Production of IL-5 in response to both extract and the Bet v1-derived peptide mix strongly suggested that T cells were a major source of IL-5.
Our explant model indicated that local presentation of antigen to resident allergen-specific Th2 cells is the early event in the pathogenesis of allergic rhinitis. These findings identify possible cellular targets for anti-inflammatory treatment.
季节性变应性鼻炎是一种由吸入性气传变应原引发的鼻黏膜慢性炎症。炎症反应由变应原特异性T细胞控制，但这些T细胞在何处以及如何被激活尚未完全明确。
我们想要确定在花粉季节之外的稳态条件下，变应原特异性辅助性T（Th）2细胞是否存在于鼻黏膜中；如果存在，这些细胞是否会因变应原刺激而在局部被激活。
从桦树或草花粉变应性鼻炎患者以及健康对照者身上，在非花粉季节获取下鼻甲的黏膜活检组织。将培养的外植体样本用相关花粉提取物或从主要桦树变应原疣皮桦（Betula verrucosa，Bet v）1序列衍生的重叠20肽混合物进行刺激。24小时后，收集培养基用于多重细胞因子和类胰蛋白酶分析。
仅在变应性组中，驻留细胞在体外变应原刺激下分泌了大量白细胞介素（IL）-5。对于所检测的其他细胞因子未观察到增加。对提取物和Bet v1衍生肽混合物均有IL-5产生，强烈提示T细胞是IL-5的主要来源。
我们的外植体模型表明，向驻留的变应原特异性Th2细胞局部呈递抗原是变应性鼻炎发病机制中的早期事件。这些发现确定了抗炎治疗可能的细胞靶点。
