Flügel Alexander, Odoardi Francesca, Nosov Mikhail, Kawakami Naoto
Max-Planck-Institute for Neurobiology, Martinsried, Germany.
J Neuroimmunol. 2007 Nov;191(1-2):86-97. doi: 10.1016/j.jneuroim.2007.09.017. Epub 2007 Oct 31.
Two photon microscopy (TPM) recently emerged as optical tool for the visualization of immune processes hundreds of micrometers deep in living tissue and organs. Here we summarize recent work on exploiting this technology to study brain antigen specific T cells. These cells are the cause of Experimental Autoimmune Encephalomyelitis (EAE) an autoimmune disease model of Multiple Sclerosis. TPM studies elucidated the dynamics of the autoaggressive effector T cells in peripheral immune milieus during preclinical EAE, where the cells become reprogrammed to enter their target organ. These studies revealed an unexpectedly lively locomotion behavior of the cells interrupted only by short-lasting contacts with the local immune stroma. Live T cell behavior was furthermore studied within the acutely inflamed CNS. Two distinct migratory patterns of the T cells were found: the majority of cells (60-70%) moved fast and seemingly unhindered through the compact CNS parenchyma. The motility of the other cell fraction was highly confined. The cells swung around a fixed cell pole forming long-lasting contacts to putative local antigen presenting cells.
双光子显微镜（TPM）最近成为一种光学工具，可用于可视化活组织和器官中数百微米深处的免疫过程。在此，我们总结了利用该技术研究脑抗原特异性T细胞的近期工作。这些细胞是实验性自身免疫性脑脊髓炎（EAE）的病因，EAE是多发性硬化症的一种自身免疫性疾病模型。TPM研究阐明了临床前EAE期间外周免疫环境中自身攻击性效应T细胞的动态变化，在此期间，这些细胞会重新编程以进入其靶器官。这些研究揭示了细胞出人意料的活跃运动行为，仅被与局部免疫基质的短暂接触所打断。此外，还在急性炎症性中枢神经系统内研究了活T细胞的行为。发现了T细胞的两种不同迁移模式：大多数细胞（60 - 70%）快速移动，似乎不受阻碍地穿过致密的中枢神经系统实质。另一部分细胞的运动性则受到高度限制。这些细胞围绕一个固定的细胞极摆动，与假定的局部抗原呈递细胞形成持久接触。
