Hamann A, Klugewitz K, Austrup F, Jablonski-Westrich D
Experimentelle Rheumatologie, Medizinische Klinik, Charité, Humboldt-Universität Berlin and Deutsches Rheumaforschungszentrum, Berlin, Germany.
Eur J Immunol. 2000 Nov;30(11):3207-18. doi: 10.1002/1521-4141(200011)30:11<3207::AID-IMMU3207>3.0.CO;2-L.
Activation and differentiation of lymphocytes have profound effects on their trafficking. Whereas naive T cells recirculate through lymphoid organs, activated cells localize predominantly in other compartments. Here, we report that changes in migratory properties of T cells occur immediately upon activation via the TCR. One hour stimulation is enough to target T cells into lung and liver following i.v. injection. The high localization within lung and liver and the lack of recirculation through lymphoid tissues are key features of activated lymphocytes. the source, in vitro as well as in vivo activated lymphocytes show this behavior, which is not caused by increased cell size. Accumulation in the lung requires protein synthesis and is partly mediated by LFA-1, in contrast to the acquisition of liver "homing" properties. Intravital microscopy reveals firm adhesion of activated cells within periportal sinusoids of the liver. Selective homing to other organs, such as skin or mucosa, was not observed, regardless of the cell's origin. These data indicate that activation quickly switches the trafficking program of lymphocytes from recirculation to sequestration; it is tempting to speculate that especially the induced trapping in the liver has a distinct role in limiting systemic T cell responses.
淋巴细胞的激活和分化对其迁移具有深远影响。未活化的T细胞在淋巴器官中循环,而活化的细胞主要定位于其他区域。在此,我们报告T细胞经TCR激活后,其迁移特性立即发生变化。静脉注射后,一小时的刺激就足以使T细胞靶向进入肺和肝脏。肺和肝脏中的高定位以及不通过淋巴组织再循环是活化淋巴细胞的关键特征。无论是体外还是体内活化的淋巴细胞均表现出这种行为,这并非由细胞体积增大所致。与获得肝脏“归巢”特性不同,肺中的聚集需要蛋白质合成,且部分由淋巴细胞功能相关抗原-1(LFA-1)介导。活体显微镜检查显示活化细胞在肝脏门静脉周围的血窦内牢固黏附。无论细胞来源如何,均未观察到其选择性归巢至其他器官,如皮肤或黏膜。这些数据表明,激活迅速将淋巴细胞的迁移程序从再循环转变为滞留;由此推测,特别是诱导性滞留在肝脏中对于限制全身性T细胞反应具有独特作用。