Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis
Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis
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DOI：
10.4049/jimmunol.172.7.4018
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Lane, TE
中科院分区：
文献类型：
--
作者：
Glass, WG;Hickey, MJ;Lane, TE
小鼠肝炎病毒（冠状病毒科成员）脑内感染小鼠可重复导致急性脑脊髓炎，并发展为慢性脱髓鞘疾病。在疾病的慢性阶段期间，随后的神经病理学主要是免疫介导的，并且类似于人类脱髓鞘疾病多发性硬化症。中枢神经系统内趋化因子的分泌发出白细胞浸润的信号，从而导致白色物质破坏和神经功能障碍。CC趋化因子配体（CCL）5定位于经历脱髓鞘的白色物质束中，表明该趋化因子通过吸引炎性细胞进入CNS而参与疾病的发病机制。在这项研究中，我们管理的单克隆抗体针对CCL 5的小鼠建立小鼠肝炎病毒诱导的脱髓鞘和受损的运动技能。抗-CCL 5治疗部分基于病毒Ag特异性降低CNS内的T细胞积累，表明差异靶向选择的T细胞群体的能力。此外，抗CCL 5给药改善了神经功能，并显著（p小于或等于0.005）降低了CNS内脱髓鞘和巨噬细胞积聚的严重程度。这些结果表明，通过在脱髓鞘病毒模型中使用针对CCL 5的中和mAb，可以降低CNS疾病的严重程度。
Intracerebral infection of mice with mouse hepatitis virus, a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis that progresses to a chronic demyelinating disease. The ensuing neuropathology during the chronic stage of disease is primarily immune mediated and similar to that of the human demyelinating disease multiple sclerosis. Secretion of chemokines within the CNS signals the infiltration of leukocytes, which results in destruction of white matter and neurological impairment. The CC chemokine ligand (CCL)5 is localized in white matter tracts undergoing demyelination, suggesting that this chemokine participates in the pathogenesis of disease by attracting inflammatory cells into the CNS. In this study, we administer a mAb directed against CCL5 to mice with established mouse hepatitis virus-induced demyelination and impaired motor skills. Anti-CCL5 treatment decreased T cell accumulation within the CNS based, in part, on viral Ag specificity, indicating the ability to differentially target select populations of T cells. In addition, administration of anti-CCL5 improved neurological function and significantly (p less than or equal to 0.005) reduced the severity of demyelination and macrophage accumulation within the CNS. These results demonstrate that the severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination.