T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules : a critical role for P-selectin glycoprotein ligand-1
T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules : a critical role for P-selectin glycoprotein ligand-1
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2003
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通讯作者：
L. Battistini;L. Piccio;Barbara Rossi;S. Bach;S. Galgani;C. Gasperini;L. Ottoboni;Donatella Ciabini;M. Caramia;G. Bernardi;C. Laudanna;E. Scarpini;R. McEver;E. Butcher;G. Borsellino;G. Constantin
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作者：
L. Battistini;L. Piccio;Barbara Rossi;S. Bach;S. Galgani;C. Gasperini;L. Ottoboni;Donatella Ciabini;M. Caramia;G. Bernardi;C. Laudanna;E. Scarpini;R. McEver;E. Butcher;G. Borsellino;G. Constantin
多发性硬化症（MS）被认为是一种中枢神经系统的自身免疫性炎症疾病。在生理条件下，我们比较了未接受治疗的急性复发缓解型多发性硬化症（RRMS）患者和健康供者的CD4和CD8淋巴细胞的粘附性。我们发现，在患有RRMS CD8而非RRMS CD4的患者中，T细胞在发炎的小鼠脑小静脉中显示出增加的滚动和停止。此外，MS患者的CD8淋巴细胞对p -选择素的滚动增加，而不是CD4淋巴细胞。抗p选择素糖蛋白配体-1 （PSGL-1）抗体可显著阻断MS患者脑血管中CD8细胞的募集，这表明PSGL-1可能是一种新的药物靶点，可用于阻断早期炎症期间CD8细胞的选择性进入。血管细胞粘附分子-1 (VCAM-1)，而不是PSGL-1，对MS患者CD4细胞的粘附至关重要，这突出了RRMS中淋巴细胞亚群募集机制的基本对立。重要的是，7色荧光激活细胞分选仪（FACS）分析以及功能数据表明，MS患者的CD8细胞中有很大一部分表现出记忆效应表型的特征。总之，我们的研究结果表明，RRMS患者在疾病急性期的CD8 T细胞，而不是CD4 T细胞，在发炎的脑小静脉中显示出增加的招募能力。(血。2003;101:4775 - 4782)
Multiple sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system. Under physiologic conditions, we compared the adhesiveness of CD4 and CD8 lymphocytes from nontreated patients with acute, relapsing-remitting multiple sclerosis (RRMS) and from healthy donors. We show that in patients with RRMS CD8 , but not with RRMS CD4 , T cells display increased rolling and arrest in inflamed murine brain venules. Moreover, CD8 , but not CD4 , lymphocytes from MS patients show increased rolling on P-selectin in vitro. Anti–P-selectin glycoprotein ligand-1 (PSGL-1) antibodies dramatically block the recruitment of CD8 cells in brain vessels of patients with MS, suggesting that PSGL-1 represents a novel pharmaceutical target that may be exploited to block the selective entrance of CD8 cells during early inflammation. Vascular cell adhesion molecule-1 (VCAM-1), but not PSGL-1, is critical for the adhesion of CD4 cells in MS patients, highlighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS. Importantly, 7-color fluorescence-activated cell sorter (FACS) analysis, together with functional data, indicates that a large fraction of CD8 cells from MS patients display the characteristics of memory-effector phenotype. In conclusion, our results show that CD8 , but not CD4 , T cells from patients with RRMS in the acute phase of the disease display increased ability to be recruited in inflamed brain venules. (Blood. 2003;101:4775-4782)