von Andrian U H, M'Rini C
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cell Adhes Commun. 1998;6(2-3):85-96. doi: 10.3109/15419069809004463.
Blood-borne lymphocytes migrate continuously to peripheral lymph nodes (PLN) and other organized lymphoid tissues where they are most likely to encounter their cognate antigen. Lymphocyte homing to PLN is a highly regulated process that occurs exclusively in specialized high endothelial venules (HEV) in the nodal paracortex. Recently, it has become possible to explore this vital aspect of peripheral immune surveillance by intravital microscopy of the subiliac lymph node microcirculation in anesthetized mice. This paper reviews technical and experimental aspects of the new model and summarizes recent advances in our understanding of the molecular mechanisms of lymphocyte homing to PLN which were derived from its use. Both lymphocytes and granulocytes initiate rolling interactions via L-selectin binding to the peripheral node addressin (PNAd) in PLN HEV. Subsequently, a G protein-coupled chemoattractant stimulus activates LFA-1 on rolling lymphocytes, but not on granulocytes. Thus, granulocytes continue to roll through the PLN, whereas LFA-1 activation allows lymphocytes to arrest and emigrate into the extravascular compartment. We have also identified a second homing pathway that allows L-selectin low/(activated/memory) lymphocytes to home to PLN. P-selectin on circulating activated platelets can mediate simultaneous platelet adhesion to PNAd in HEV and to P-selectin glycoprotein ligand (PSGL)-1 on lymphocytes. Through this mechanism, platelets can form a cellular bridge which can effectively substitute for the loss of L-selectin on memory cell subsets.
血源性淋巴细胞持续迁移至外周淋巴结（PLN）和其他有组织的淋巴组织，在这些地方它们最有可能遇到其同源抗原。淋巴细胞归巢至PLN是一个高度受调控的过程，仅发生在淋巴结副皮质区的特殊高内皮微静脉（HEV）中。最近，通过对麻醉小鼠的髂下淋巴结微循环进行活体显微镜观察，得以探究外周免疫监视的这一重要方面。本文回顾了该新模型的技术和实验方面，并总结了我们对淋巴细胞归巢至PLN的分子机制的最新认识进展，这些进展源自对该模型的应用。淋巴细胞和粒细胞均通过L选择素与PLN的HEV中的外周淋巴结地址素（PNAd）结合来启动滚动相互作用。随后，一种G蛋白偶联趋化因子刺激激活滚动淋巴细胞上的LFA-1，但不激活粒细胞上的LFA-1。因此，粒细胞继续在PLN中滚动，而LFA-1的激活使淋巴细胞能够停滞并迁移到血管外间隙。我们还确定了第二条归巢途径，该途径允许L选择素低表达/（活化/记忆）淋巴细胞归巢至PLN。循环活化血小板上的P选择素可介导血小板同时黏附于HEV中的PNAd和淋巴细胞上的P选择素糖蛋白配体（PSGL）-1。通过这种机制，血小板可形成一个细胞桥，该细胞桥可有效替代记忆细胞亚群上L选择素的缺失。
