Expression of the T cell receptor Vβ repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases

Expression of the T cell receptor Vβ repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases
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DOI:
10.1177/039463200601900409
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发表时间:
2006-10-01
影响因子:
3.5
通讯作者:
Otsuki, T.
Otsuki, T.
中科院分区:
医学4区
文献类型:
--
作者:
Nishimura, Y.;Miura, Y.;Otsuki, T.

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为探讨石棉和二氧化硅对人体免疫系统的影响,采用人HTLV-1永生化多克隆T细胞系MT-2(MT-2 T)建立了低剂量长期接触石棉和二氧化硅的实验模型。MT-2细胞连续暴露于石棉,其浓度(10 μ g/ml)在短期暴露期间不诱导完全细胞死亡。在获得对CB诱导的细胞凋亡的抗性(命名为MT-2 Rst)后,在MT-2 Rst和MT-2 Rst系之间就T细胞受体-V β(Tc β-V β)表达进行免疫学比较。MT-2 Rst细胞表现出各种TcR-V β的过量表达,尽管TcR-V β过量呈递细胞的特征在于由于首次与CB接触而经历凋亡。将石棉相关疾病(ARD)患者(如石棉沉着病和恶性间皮瘤)与矽肺(SIL)患者(作为疾病对照)和健康供体(HD)进行比较。SIL和ARD不仅在它们的致病材料(作为矿物硅酸盐的二氧化硅和石棉)方面不同,而且在并发症方面也不同; SIL中的自身免疫性疾病和ARD中的肿瘤。ARD患者表现出TcR-V β的限制性过度表达而无克隆扩增,而SIL患者表现出TcR-V β 7.2的显著过度表达。这些实验和临床分析表明,超抗原和失调的自身免疫诱导作用的石棉和二氧化硅,分别。
To explore the effects of asbestos and silica on the human immune system, an experimental model of low-dose and long-term exposure was established using a human HTLV-1-immortalized polyclonal T cell line, MT-2 (MT-2Org). MT-2 cells were continuously exposed to asbestos at a concentration (10 mu g/ml) which does not induce complete cell death during short-term exposure. After acquiring resistance to CB-induced apoptosis (designated MT-2Rst), an immunological comparison was made between the MT-2Org and MT-2Rst lines in terms of T cell receptor-V beta (Tc beta-V beta) expression. MT-2Rst cells showed excess expression of various TcR-V beta, although TcR-V beta-overpresenting cells were characterized as undergoing apoptosis due to first contact with CB. Patients with asbestos-related diseases (ARD), such as asbestosis and malignant mesothelioma, were compared with silicosis (SIL) patients as a disease control and with healthy donors (HD). SIL and ARD not only differed in their causative materials, silica and asbestos as mineral silicates, but also in terms of complications; autoimmune disorders in SIL and tumors in ARD. ARD patients showed a restricted overpresentation of TcR-V beta without clonal expansion, whereas SIL patients revealed significant overpresentation of TcR-V beta 7.2. These experimental and clinical analyses indicate the superantigenic and dysregulation of autoimmunity-inducing effects of asbestos and silica, respectively.