Delon Jérôme, Stoll Sabine, Germain Ronald N
Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
Immunol Rev. 2002 Nov;189:51-63. doi: 10.1034/j.1600-065x.2002.18906.x.
The development of an effective immune response requires cell-cell contact between T cells and antigen-bearing cells of several types (dendritic cells, B cells, infected tissue cells). Recent advances in light microscopy have led to intense investigation of the molecular events that accompany these cell interactions, especially the redistribution of membrane proteins into discrete organized subdomains within the zone of cell-cell contact termed the 'immunological synapse'. Here we discuss two aspects of our own studies in this area. First, we highlight results from our in vitro analysis of the role of the cytoskeletal ezrin, radixin, moesin adapter proteins in the exclusion of CD43 from the well-defined T cell receptor (TCR) and integrin-rich zones of the synapse. Based on the molecular mechanism uncovered in this work, we propose a new model for how TCR-signaled changes in cytoskeletal organization indirectly influence both protein distributions and the efficiency of signaling between T cell and presenting cell. We then discuss the development of a new method for dynamic visualization of T cell - dendritic cell interactions in intact lymphoid tissue. The remarkable longevity of monogamous lymphocyte-presenting cell interactions is discussed, differences between our observations and those of others are laid out in detail, and prospects for future application of this technical approach to analysis of early immune responses in lymphoid organs and of effector lymphocyte function in tissues are presented.
有效的免疫反应的发展需要T细胞与几种类型的抗原呈递细胞（树突状细胞、B细胞、受感染的组织细胞）之间的细胞间接触。光学显微镜技术的最新进展引发了对伴随这些细胞相互作用的分子事件的深入研究，尤其是膜蛋白重新分布到细胞间接触区域内离散的有组织的亚结构域，即所谓的“免疫突触”。在此，我们讨论我们在该领域自身研究的两个方面。首先，我们重点介绍我们在体外分析细胞骨架埃兹蛋白、根蛋白、膜突蛋白衔接蛋白在将CD43排除在突触中明确界定的T细胞受体（TCR）和富含整合素的区域方面所起作用的研究结果。基于这项工作中揭示的分子机制，我们提出了一个新模型，说明TCR信号传导引起的细胞骨架组织变化如何间接影响蛋白质分布以及T细胞与呈递细胞之间信号传导的效率。然后，我们讨论了一种用于动态可视化完整淋巴组织中T细胞与树突状细胞相互作用的新方法。我们讨论了一夫一妻制淋巴细胞与呈递细胞相互作用的显著持久性，详细阐述了我们的观察结果与其他人的观察结果之间的差异，并介绍了这种技术方法未来应用于分析淋巴器官早期免疫反应和组织中效应淋巴细胞功能的前景。
