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

金属过敏被归类为一种延迟型超敏反应，其特征是淋巴细胞募集到过敏性炎症部位。由于缺乏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未被探讨。因此，我们开发了一种新的小鼠模型，通过多次注射钯（Pd）和脂多糖到足垫，研究与T细胞浸润相关的金属过敏。利用该模型，我们从表型标记、T细胞受体（TCR）谱和细胞因子表达等方面对足底浸润T细胞进行了表征。Pd刺激后7天，过敏足垫中CD3+CD4+ T细胞积累。刺激后足垫中CD25、白细胞介素-2、干扰素-γ和肿瘤神经坏死因子的表达水平升高，但白细胞介素-4和白细胞介素-5的表达水平不升高，提示CD4+ T辅助1 （Th1）细胞在Pd作用下局部扩增。与淋巴结T细胞相比，足垫浸润T细胞频繁表达AV18-1和BV8-2 TCR链，并表现出低克隆性。从几种pd诱导小鼠克隆型的TCR具有相同或相似的含有AV18-1的CDR3序列，但在BV8-2中具有不同的序列。这些结果表明，tcr α-链在pd特异性Th1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.