Peripheral blood CD4+T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line
Peripheral blood CD4+T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line
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DOI：
10.1189/jlb.1008666
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发表时间：
2009-11-01
影响因子：
5.5
通讯作者：
Soulillou, Jean-Paul
中科院分区：
文献类型：
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作者：
Bahbouhi, Bouchaib;Berthelot, Laureline;Soulillou, Jean-Paul
MS中T淋巴细胞在脑中的运输机制尚不清楚。我们假设MS与增加的CD 4+和CD 8 + T淋巴细胞在BBB中的运输有关。为了验证这一假设，我们计算了27名RR-MS患者（21名未经治疗，6名IFN-β治疗）和18名HI患者PBMC中PSGL-1+/CD 4+和PSGL-1+ CD 8+或LFA-1+/CD 4 +/CD 8 + T细胞的频率。接下来，我们在静态条件下测量了它们在静息和TNF-α活化的人BBB衍生的hCMEC/D3内皮层上的离体TR。MS患者PSGL-1+ CD 4 + T淋巴细胞的频率在治疗或未治疗的MS患者中显著高于HI。此外，来自治疗或未治疗的MS患者的CD 4+淋巴细胞（纯化的或在PBMC中）的静息hCMEC/D3 TR显著高于HI的那些，并且与其移行组分中的CD 4 +PSGL+或CD 4 +PSGL-1+ CD 45 RO + T细胞的显著富集相关。在TNF-α激活的hCMEC/D3中，MS患者的CD 4+和CD 8+的TR也显著高于HI中观察到的TR。在所有组中，抗PSGL-1/抗LFA-1均显著阻断静息hCMEC/D3的迁移，并且抗VLA-4特异性地抑制MS T细胞的迁移。纯化的PSGL-1-阴性CD 4+淋巴细胞与静息hCMEC/D3一起迁移
Mechanisms of T lymphocyte trafficking in the brain remain unclear in MS. We hypothesized that MS is associated with increased CD4+ and CD8+ T lymphocyte trafficking across the BBB. To test this hypothesis, we calculated the frequency of PSGL-1+/CD4+ and PSGL-1+CD8+ or LFA-1+/CD4+/CD8+ T cells in the PBMC of 27 patients with a RR-MS (21 untreated and six IFN-beta-treated) and 18 HI. Next, we measured their ex vivo TR across resting and TNF-alpha-activated human BBB-derived hCMEC/D3 endothelial layers under static conditions. The frequency of PSGL-1+CD4+ T lymphocytes was significantly higher in treated or untreated MS patients than HI. Furthermore, resting hCMEC/D3 TR of CD4+ lymphocytes (purified or in PBMC) from treated or untreated MS patients were significantly higher than those of HI and associated with significant enrichments of CD4+PSGL+ or CD4+PSGL-1+CD45RO+ T cells in their transmigrating fractions. The TR of CD4+ and CD8+ from MS patients across TNF-alpha-activated hCMEC/D3 were also significantly higher than that observed in HI. Resting hCMEC/D3 transmigration was blocked significantly by anti-PSGL-1/anti-LFA-1 in all groups, and anti-VLA-4 inhibited transmigration of MS T cells specifically. Purified PSGL-1-negative CD4+ lymphocytes transmigrated resting hCMEC/D3 with