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

Chracterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine models of Palladium-induced metal allergy
钯诱导金属过敏新型小鼠模型浸润发炎皮肤的 Th1 细胞 T 细胞受体的表征
批准号:
22791823
负责人:
GOTOU Akito
金额:
$2.5万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Young Scientists (B)
财政年份:
2010
资助国家:
日本
项目状态:
已结题
起止时间:
2010 至 2012

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中文摘要
翻译
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。
英文摘要
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.
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DOI: --
发表时间: 2010
期刊:
影响因子: --
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DOI: 10.1038/ijos.2013.10
发表时间: 2013-03
期刊: INTERNATIONAL JOURNAL OF ORAL SCIENCE
影响因子: 14.9
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DOI: --
发表时间: 2012
期刊:
影响因子: --
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DOI: 10.1016/j.jim.2012.07.012
发表时间: 2012-10
期刊: Journal of immunological methods
影响因子: 2.2
作者: [Kazutaka Kitaura;Yoshiki Fujii;T. Matsutani;K. Shirai;S. Suzuki;T. Takasaki;S. Shimada;Y. Kametani;T. Shiina;Shuji Takabayashi;H. Katoh;K. Ogasawara;I. Kurane;R. Suzuki]
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