Johnson Trina A, Lapierre Yves, Bar-Or Amit, Antel Jack P
Montreal Neurological Institute, QC, Canada.
Arch Neurol. 2010 Dec;67(12):1449-55. doi: 10.1001/archneurol.2010.312.
To define the capacity of peripheral blood CD8(+) T cells from patients with multiple sclerosis (MS) receiving fingolimod (FTY720) to migrate in response to chemokines that contribute to trafficking into the central nervous system.
Peripheral blood T cells of FTY720-treated patients with MS (MS-FTY) are mainly CD8(+) CCR7⁻ effector memory cells as CCR7(+) T cells are inhibited from exiting from secondary lymph nodes. Migration of CD8(+) T cells from MS-FTY patients and untreated donors to chemokines CXCL12 and CCL2 was assayed in vitro. Expression of CCL2 receptor (CCR2), CCR7, CD28, and CD27 on CD8(+) T cells was determined by flow cytometry.
Montreal Neurological Institute's clinical research unit. Patients The MS-FTY patients were part of the extension phase of FTY720 clinical trials for relapsing-remitting MS.
In vitro addition of active (phosphorylated) FTY720 increased migration of CD8(+) T cells from untreated patients to CXCL12 and CCL2. The CD8(+) or CD8(+) CCR7⁻ T cells from MS-FTY patients migrated less to CXCL12 and CCL2 compared with those from untreated donors. The proportion of CD8(+) CCR7⁻ cells that express the CCL2 chemokine receptor, CCR2, was significantly reduced in the MS-FTY group. The CD8(+) CCR7⁻ cells from the MS-FTY patients were enriched with CD27⁻ CD28⁻ (late effector) memory cells, a population with reduced expression of CCR2 compared with early (CD27(+) CD28(+)) effector memory cells.
Therapy with FTY720 results in a subset of CD8(+) T cells with distinct functional migratory properties dominating the peripheral circulation. The expected forthcoming use of FTY720 as a sustained therapy for MS will clarify how this redistribution of lymphocyte populations affects the overall process of immune surveillance.
确定接受芬戈莫德（FTY720）治疗的多发性硬化症（MS）患者外周血CD8(+) T细胞对有助于其向中枢神经系统迁移的趋化因子作出反应而发生迁移的能力。
接受FTY720治疗的MS患者（MS-FTY）的外周血T细胞主要是CD8(+) CCR7⁻效应记忆细胞，因为CCR7(+) T细胞被抑制从二级淋巴结中逸出。在体外检测了MS-FTY患者和未治疗供体的CD8(+) T细胞对趋化因子CXCL12和CCL2的迁移情况。通过流式细胞术测定CD8(+) T细胞上CCL2受体（CCR2）、CCR7、CD28和CD27的表达。
蒙特利尔神经病学研究所临床研究室。患者：MS-FTY患者是FTY720治疗复发缓解型MS临床试验扩展阶段的一部分。
体外添加活性（磷酸化）FTY720可增加未治疗患者的CD8(+) T细胞向CXCL12和CCL2的迁移。与未治疗供体的细胞相比，MS-FTY患者的CD8(+)或CD8(+) CCR7⁻ T细胞向CXCL12和CCL2的迁移较少。MS-FTY组中表达CCL2趋化因子受体CCR2的CD8(+) CCR7⁻细胞比例显著降低。MS-FTY患者的CD8(+) CCR7⁻细胞富含CD27⁻ CD28⁻（晚期效应）记忆细胞，与早期（CD27(+) CD28(+)）效应记忆细胞相比，该群体中CCR2的表达降低。
FTY720治疗导致具有独特功能迁移特性的CD8(+) T细胞亚群在外周循环中占主导地位。FTY720即将作为MS的持续治疗药物使用，这将阐明淋巴细胞群体的这种重新分布如何影响免疫监视的整体过程。
