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: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• 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
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791823/
• 关键词: 免疫; 感染; 炎症; 金属アレルギー; TCR; 遅延型過敏反応

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.

金属过敏被归类为迟发型超敏反应，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得到探讨。因此，我们开发了一种新的小鼠模型，金属过敏与T细胞浸润的钯（Pd）加脂多糖多次注射到足垫。使用这个模型，我们的特点是足垫浸润T细胞的表型标志物，T细胞受体（TCR）的剧目和细胞因子的表达。Pd激发后7天，CD 3 + CD 4 + T细胞聚集在过敏足垫中。CD 25、IL-2、IFN-γ和肿瘤坏死因子的表达水平升高，但IL-4和IL-5的表达水平没有升高，提示CD 4 + Th 1细胞在局部扩增。与淋巴结中的T细胞相比，足垫中的浸润T细胞经常表达AV 18 -1和BV 8 -2 TCR链，并表现出寡克隆性。从几只Pd诱导的小鼠中鉴定的TCR克隆型共有相同或相似的含有AV 18 -1的CDR 3序列，但在BV 8 -2中具有不同的序列。这些结果表明TCRα链在Pd特异性Th 1细胞的抗原特异性中起主导和关键作用。

项目成果

口腔扁平苔癬におけるEGFRシグナル伝達機構の解明

口腔扁平苔藓中 EGFR 信号传导机制的阐明

• 发表时间: 2010
• 作者: 熊谷賢一;堀川達弥;後藤哲人;山田浩之;小林浩;江口貴紀;濱田良樹;鈴木隆二
• 通讯作者: 鈴木隆二

新規金属アレルギーモデルマウスにおける網羅的T 細胞レセプター解析

新型金属过敏模型小鼠的 T 细胞受体综合分析

• 发表时间: 2012
• 作者: 小林浩;江口貴紀;熊谷賢一;重松宏昭,後藤哲人;濱田良樹;鈴木隆二
• 通讯作者: 鈴木隆二

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia.

• 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
• 作者: Kobayashi, Hiroshi;Kumagai, Kenichi;Gotoh, Akito;Eguchi, Takanori;Yamada, Hiroyuki;Hamada, Yoshiki;Suzuki, Satsuki;Suzuki, Ryuji
• 通讯作者: Suzuki, Ryuji

A new method for quantitative analysis of the T cell receptor V region repertoires in healthy common marmosets by microplate hybridization assay.

• 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

Increased positive selection pressure within the complementarity determining regions of the T‐cell receptor β gene in New World monkeys

新世界猴 T 细胞受体 β 基因互补性决定中阳性区域选择压力增加

• 发表时间: 2011
• 期刊: American Journal of Primatology
• 影响因子: 2.4
• 作者: T. Matsutani;Yoshiki Fujii;Kazutaka Kitaura;S. Suzuki;Y. Tsuruta;T. Takasaki;K. Ogasawara;N. Nishimoto;I. Kurane;R. Suzuki
• 通讯作者: R. Suzuki