Chracterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine models of Palladium-induced metal allergy

金属过敏被归类为迟发性超敏反应，其特征是淋巴细胞重新聚集到过敏性炎症部位。由于目前尚无合适的金属过敏动物模型，T细胞在金属过敏发病机制中的作用尚不清楚。因此，我们建立了一种新的小鼠金属过敏模型，通过向足垫多次注射钯(PD)和脂多糖，与T细胞的渗透相关。利用这个模型，我们从表型标记物、T细胞受体(TCR)谱系和细胞因子表达等方面对足垫浸润性T细胞进行了表征。PD攻击后7d，CD3+CD4+T细胞在变态反应足垫内大量聚集。CD2 5、IL-2、干扰素-γ和肿瘤坏死因子的表达水平在激发后升高，而IL-4和IL-5的表达水平无明显变化，提示CD4+T辅助细胞1(Th1)细胞局部扩增是对PD的反应。与淋巴结中的T细胞相比，足垫浸润性T细胞表达AV18-1和BV8-2 TCR链的频率更高，并表现出寡克隆性。从几个PD诱导的小鼠中鉴定出的TCR克隆型具有相同或相似的包含AV18-1的CDR3序列，但在BV8-2中具有不同的序列。这些结果表明，TCRTh1链在PD特异性α细胞的抗原特异性中起主导和关键作用。

Metal allergy is categorized as a delayed-type hypersensitivity reaction, and is characterized by the recruitment of lymphocytes into sites of allergic inflammation. Because of the unavailability of suitable animal models for metal allergy, the role of T cells in the pathogenesis of metal allergy has not been explored. Thus, we developed a novel mouse model for metal allergy associated with infiltration of T cells by multiple injections of palladium(Pd) plus lipopolysaccharide into the footpad. Using this model, we characterized footpad-infiltrating T cells in terms of phenotypic markers, T cell receptor(TCR) repertoires and cytokine expression. CD3+CD4+ T cells accumulated in the allergic footpads 7 days after Pd challenge. The expression levels of CD25, interleukin-2, interferon-γ and tumor nevrosis facter, but not interleukin-4 and interleukin-5, increased in the footpads after challenge, suggesting CD4+ T helper 1 (Th1) cells locally expanded in response to Pd. Infiltrated T cells in the footpads frequently expressed AV18-1 and BV8-2 TCR chains compared with T cells in the lymph nodes and exhibited oligoclonality. TCR clonotyped identified from several Pd-induced mice shared identical or similar CDR3 sequences containing AV18-1, but had diverse sequences in BV8-2. These results suggest that TCRα-chains play a dominant and critical role in antigen specificity of Pd-specific Th1 cells.