Sathiyanadan Karthik, Coisne Caroline, Enzmann Gaby, Deutsch Urban, Engelhardt Britta
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Eur J Immunol. 2014 Aug;44(8):2287-94. doi: 10.1002/eji.201344214. Epub 2014 May 11.
T-cell migration across the blood-brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P-selectin glycoprotein ligand-1 (PSGL-1) and its endothelial ligands E- and P-selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL-1 or E/P-selectins does not result in ameliorated EAE, we speculated that T-cell entry into the spinal cord is independent of PSGL-1 and E/P-selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL-1(-/-) proteolipid protein-specific T cells in inflamed spinal cord microvessels of WT or E/P-selectin(-/-) SJL/J mice during EAE. T-cell rolling but not T-cell capture was completely abrogated in the absence of either PSGL-1 or E- and P-selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T-cell invasion into the CNS parenchyma. Thus, PSGL-1 interaction with E/P-selectin is essential for T-cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T-cell rolling is not required for successful T-cell entry into the CNS and initiation of EAE.
T细胞穿越血脑屏障是实验性自身免疫性脑脊髓炎（EAE，一种多发性硬化症的动物模型）发病机制中的关键步骤。活细胞成像研究表明，P-选择素糖蛋白配体-1（PSGL-1）及其内皮配体E-选择素和P-选择素介导了EAE期间T细胞在脑血管中的初始滚动。由于PSGL-1或E/P-选择素功能缺失并未导致EAE病情改善，我们推测T细胞进入脊髓独立于PSGL-1和E/P-选择素。通过活体显微镜检查，我们观察了EAE期间野生型或PSGL-1基因敲除（-/-）的蛋白脂蛋白特异性T细胞与野生型或E/P-选择素基因敲除（-/-）的SJL/J小鼠炎症脊髓微血管之间的相互作用。在缺乏PSGL-1或E-选择素和P-选择素的情况下，T细胞滚动而非T细胞捕获完全被消除，导致能够牢固黏附在炎症脊髓微血管中的T细胞数量显著减少，但并未导致T细胞侵入中枢神经系统实质减少。因此，PSGL-1与E/P-选择素的相互作用对于EAE期间炎症脊髓微血管中的T细胞滚动至关重要。结合先前的观察结果，我们的研究结果表明，T细胞成功进入中枢神经系统并引发EAE并不需要T细胞滚动。
