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Activation of intra-epithelial lymphocytes; Their morphology, marker expression and ultimate fate

机译:上皮内淋巴细胞的激活;它们的形态,标志物表达和最终命运

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Intraepithelial lymphocytes (IELs) have been considered to play a key role in the defense system of the small intestine. Its mechanism has not been made sufficiently clear. Studies on IELs have been extremely limited to functions of αβ T-cell receptor (αβTCR) IELs (αβ-IELs). Since, in the mouse duodenum and jejunum, γδ-IELs consist 75 % of IELs, it thus would be inappropriate to argue the mechanism without extensive discussions over the functions of γδ-IELs. In previous studies, we found that the anti-CD3 monoclonal antibody (mAb) injection induced DNA fragmentation in intestinal epithelial cells (IECs) and DNA repair immediately after, that these responses were reproduced by anti-γδTCR mAb not by anti-αβTCR mAb and that the DNA fragmentation was induced by Granzyme B secreted by IELs, totally independent of Perforin. To further explore the functions of IELs in situ, we undertook experiments exclusively focused on IELs, on their changes and ultimate fate after the stimulation in mouse in vivo system. The current study demonstrated that the injected anti-CD3 mAb bound to CD3 on IELs, that the mAb activated γδ-IELs, leading to their degranulation, that changes occurred irreversibly in IELs and finally that activated IELs died in situ. γδ-IELs could be considered to respond to various stimulations most likely without the need of accessory cells ("always ready for rapid response"), to die in situ ("disposable") and thus to respond to the stimulation only once ("a one-shot responder"). These characteristics of γδ-IELs are important to further elucidate the functions of γδ-IELs in the intestinal defense system.
机译:上皮内淋巴细胞(IEL)已被认为在小肠防御系统中起着关键作用。其机制还不够清楚。对IEL的研究非常限于αβT细胞受体(αβTCR)IEL(αβ-IEL)的功能。由于在小鼠十二指肠和空肠中,γδ-IEL占IEL的75%,因此,不对γδ-IEL的功能进行广泛讨论就不宜争论该机制。在先前的研究中,我们发现抗CD3单克隆抗体(mAb)注射后立即在肠道上皮细胞(IECs)中引起DNA片段化和DNA修复,这些反应是由抗γδTCRmAb而非由抗αβTCRmAb和DNA片段化是由IEL分泌的粒酶B诱导的,完全独立于穿孔素。为了进一步探索IEL的原位功能,我们进行了专门针对IEL的实验,这些实验是在小鼠体内系统刺激后它们的变化和最终命运。当前的研究表明,注入的抗CD3 mAb与IEL上的CD3结合,mAb活化的γδ-IEL导致其脱粒,IEL中不可逆地发生变化,最后活化的IEL死亡。可以认为γδ-IEL对各种刺激最有可能不需要辅助细胞(“总是准备快速反应”)做出响应,就地死亡(“一次性”),因此仅对刺激做出一次响应(“ a”一键响应”)。 γδ-IEL的这些特征对于进一步阐明γδ-IEL在肠道防御系统中的功能非常重要。

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