人体神经组织拥有一层严密的保护膜,但是一些免疫细胞仍能穿透保护膜进入神经系统,有时还会因此引发疾病。德国科研人员日前报告说,他们利用新技术拍摄到免疫细胞入侵神经系统的全过程。
德国马克斯·普朗克神经生物学研究所等机构的科研人员在英国《自然》杂志网站上报告说,他们用绿色荧光蛋白为一种免疫细胞——T细胞打上标记,将其放进实验鼠的血管内,尔后利用“双光子成像”技术,跟踪被标记细胞在实验鼠机体内的运动过程。
研究人员发现,T细胞入侵神经系统的过程可分为几个步骤:首先它会在血管中游动,并且可以逆血流方向运动,检查血管内壁是否有异物。然后它能穿过血管与神经系统交界处的隔离膜,并检查血管外壁和神经膜等组织。最后,当T细胞遇到一种吞噬细胞时,就会发生不正常的免疫反应,攻击神经系统,造成多发性硬化症等疾病。
“双光子成像”技术即通过探测样品经双光子激发后发出的荧光,实现样品三维成像的技术。参与上述实验的研究者说,用该技术拍摄到生动直观的T细胞活动影像,不仅纠正了过去对这方面的一些错误认识,而且大大增进了对相关疾病发病原因的理解,有助于研发针对多发性硬化症等神经系统疾病的治疗手段。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature advance online publication 14 October 2009 | doi:10.1038/nature08478
Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions
Ingo Bartholom?us1,7, Naoto Kawakami1,7, Francesca Odoardi1,2,3, Christian Schl?ger1,2, Djordje Miljkovic1, Joachim W. Ellwart4, Wolfgang E. F. Klinkert1, Cassandra Flügel-Koch5, Thomas B. Issekutz6, Hartmut Wekerle1 & Alexander Flügel1,2,3
1 Max Planck Institute for Neurobiology, 82152 Martinsried, Germany
2 Department of Neuroimmunology, Institute for Multiple Sclerosis Research, Gemeinnützige Hertie-Stiftung and University Medical Centre G?ttingen, 37073 G?ttingen, Germany
3 Institute for Immunology, Ludwig-Maximilians-University, 80336 Munich, Germany
4 Institute for Experimental Hematology, Helmholtz Centre, 81377 Munich, Germany
5 Institute for Anatomy 2, Friedrich-Alexander-University, 91054 Erlangen, Germany
6 Division of Immunology, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada
7 These authors contributed equally to this work.
Correspondence to: Hartmut Wekerle1Alexander Flügel1,2,3 Correspondence and requests for materials should be addressed to A.F. or H.W.
The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks1. Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.